[Senate Hearing 107-87]
[From the U.S. Government Publishing Office]
S. Hrg. 107-87
BLOOD CANCERS
=======================================================================
HEARING
before a
SUBCOMMITTEE OF THE
COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE
ONE HUNDRED SEVENTH CONGRESS
FIRST SESSION
__________
SPECIAL HEARING
JUNE 21, 2001--WASHINGTON, DC
__________
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COMMITTEE ON APPROPRIATIONS \1\
ROBERT C. BYRD, West Virginia, Chairman
DANIEL K. INOUYE, Hawaii TED STEVENS, Alaska
ERNEST F. HOLLINGS, South Carolina THAD COCHRAN, Mississippi
PATRICK J. LEAHY, Vermont ARLEN SPECTER, Pennsylvania
TOM HARKIN, Iowa PETE V. DOMENICI, New Mexico
BARBARA A. MIKULSKI, Maryland CHRISTOPHER S. BOND, Missouri
HARRY REID, Nevada MITCH McCONNELL, Kentucky
HERB KOHL, Wisconsin CONRAD BURNS, Montana
PATTY MURRAY, Washington RICHARD C. SHELBY, Alabama
BYRON L. DORGAN, North Dakota JUDD GREGG, New Hampshire
DIANNE FEINSTEIN, California ROBERT F. BENNETT, Utah
RICHARD J. DURBIN, Illinois BEN NIGHTHORSE CAMPBELL, Colorado
LARRY CRAIG, Idaho
KAY BAILEY HUTCHISON, Texas
JON KYL, Arizona
Terry Sauvain, Staff Director
Charles Kieffer, Deputy Staff Director
Steven J. Cortese, Minority Staff Director
------
Subcommittee on Departments of Labor, Health and Human Services, and
Education, and Related Agencies
TOM HARKIN, Iowa ARLEN SPECTER, Pennsylvania
ERNEST F. HOLLINGS, South Carolina THAD COCHRAN, Mississippi
DANIEL K. INOUYE, Hawaii JUDD GREGG, New Hampshire
HARRY REID, Nevada LARRY CRAIG, Idaho
HERB KOHL, Wisconsin KAY BAILEY HUTCHISON, Texas
PATTY MURRAY, Washington TED STEVENS, Alaska
DIANNE FEINSTEIN, California JON KYL, Arizona
ROBERT C. BYRD, West Virginia
(Ex officio)
Professional Staff
Ellen Murray
Jim Sourwine
Mark Laisch
Adrienne Hallett
Erik Fatemi
Adam Gluck
Bettilou Taylor (Minority)
Mary Dietrich (Minority)
Administrative Support
Carole Geagley
Correy Diviney (Minority)
\1\ Committee and subcommittee memberships--June 6, 2001 to July
10, 2001. Senate committee and subcommittee assignments reverted to
that which had been in existence at the conclusion of the 106th
Congress.
Note.--From January 3 to January 20, 2001 the Democrats held the
majority, thanks to the deciding vote of outgoing Democratic Vice
President Al Gore. Senator Thomas A. Daschle became majority leader at
that time. Starting January 20, 2001, the incoming Republican Vice
President Richard Cheney held the deciding vote, giving the majority to
the Republicans. Senator Trent Lott resumed his position as majority
leader. On May 24, 2001, Senator James Jeffords of Vermont announced
his switch from Republican to Independent status, effective June 6,
2001. Jeffords announced that he would caucus with the Democrats,
changing control of the evenly divided Senate from the Republicans to
the Democrats. Senator Thomas A. Daschle became majority leader once
again on June 6, 2001.
C O N T E N T S
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Page
Opening statement of Senator Tom Harkin.......................... 1
Statement of Richard Klausner, M.D., Director, National Cancer
Institute, National Institutes of Health, Department of Health
and Human Services............................................. 3
New therapies.................................................... 4
Prepared statement of Richard Klausner 5
What are leukemia, lymphoma, and multiple myeloma?............... 5
Moving toward a new understanding of LLM......................... 6
Causes, risk factors, and epidemiology of LLM.................... 7
New strategies for treatment of LLM.............................. 8
Statement of Senator Arlen Specter............................... 12
Statement of Senator Kay Bailey Hutchison........................ 14
Statement of Senator Patty Murray................................ 15
Statement of Senator Barbara A. Mikulski......................... 21
Statement of Sandra J. Horning, M.D., Stanford University School
of Medicine.................................................... 21
Prepared statement........................................... 23
A Lymphoma primer................................................ 24
Lymphoma subtypes................................................ 24
Current treatment options and treatment advances................. 24
Challenges for clinical research in lymphoma..................... 25
Role of industry in clinical research............................ 25
Research recommendations of the LLM-PRG.......................... 26
Recommendations for congressional action......................... 26
Statement of Larry Lucchino, President and CEO, San Diego Padres. 27
Prepared statement........................................... 28
Treatment for non-Hodgkin's lymphoma............................. 29
Advances in lymphoma research.................................... 29
Convening of a blue ribbon panel................................. 29
Action on the recommendations.................................... 30
Statement of Miles S. Pendleton, Jr.............................. 30
Prepared statement........................................... 32
Statement of Hagop M. Kantarjian, M.D., Chairman, Leukemia
Department, M.D. Anderson Cancer Center........................ 35
Prepared statement........................................... 36
Background....................................................... 36
Current status and progress in leukemias......................... 36
What are targeted therapies...................................... 37
Future hopes, expectations and needs............................. 37
A brief glimpse at the leukemia program at M.D. Anderson Cancer
Center......................................................... 37
Statement of Senator Ted Stevens................................. 37
Statement of Geraldine Ferraro, former Member of Congress from
New York....................................................... 42
Prepared statement........................................... 46
Statement of Kathryn E. Giusti, President, Multiple Myeloma
Research Foundation............................................ 49
Prepared statement........................................... 50
Statement of Kenneth C. Anderson, M.D., Professor of Medicine,
Harvard Medical School......................................... 51
Prepared statement........................................... 53
Statement of John W. Holaday, Ph.D., Chairman and CEO, Entremed,
Inc............................................................ 55
Prepared statement........................................... 56
Prepared statement of Beverly S. Mitchell, M.D., President,
American Society of Hematology................................. 60
Prepared statement of Howard B. Urnovitz, Ph.D., Scientific
Director, Chronic Illness Research Foundation and Chief Science
Officer, Chronix Biomedi-
cal............................................................ 62
Prepared statement of Mrs. Rafael Mora........................... 62
BLOOD CANCERS
----------
THURSDAY, JUNE 21, 2001
U.S. Senate,
Subcommittee on Labor, Health and Human
Services, and Education, and Related Agencies,
Committee on Appropriations,
Washington, DC.
The subcommittee met at 9:35 a.m., in room SD-124, Dirksen
Senate Office Building, Hon. Tom Harkin presiding.
Present: Senators Harkin, Murray, Specter, Stevens, and
Hutchison.
Also present: Senator Mikulski.
opening statement of senator tom harkin
Senator Harkin. Good morning and welcome to today's
subcommittee hearing on blood cancers.
Before I begin, my staff has informed me we have about 300
people lined up in the hallway outside. This was the only
hearing room that we could obtain today, and as you know, it is
very cramped for space. So, if I could ask everyone to please
have a seat. If we have extra spaces, we will be able to let
some more people in.
Also, I would like to ask for your indulgence. If you are
here on a panel and you are here to listen to a certain panel,
if after that panel is finished, if you would be so kind as to
perhaps remove yourself from the room and let others come in.
There are a lot of people out there who would like to come in
and participate in this hearing. So, I would just ask if you
could do that, I know there are a lot of people out there who
would really appreciate it, and I would appreciate that.
This is my first hearing as chairman since 1994, and I
would like to start first by thanking Senator Specter for the
tremendous work he has done over the past 6 years.
Right now there is a vote on the Senate floor. I think it
started at 9:30. I will make my opening statement and proceed,
and then as soon as Senator Specter shows up, I will leave to
go vote and then he will chair the hearing.
But even in his absence, I want to say that he and I have
switched back and forth between chairman and ranking member
since 1989, and we have been partners every step of the way.
I remember back in the early days when everyone thought we
were crazy for wanting to double the NIH budget within 5 years.
Now we are halfway to that goal, thanks in large part to our
bipartisan teamwork.
Senator Specter and I have also worked together on
education, worker rights, stem cell research, and many other
important issues. That is not going to change just because I am
the chairman now and he is the ranking member. He will continue
to be a leader on the subcommittee and I will continue to seek
his advice and support and friendship for years to come.
So, I publicly want to applaud Senator Specter for his
leadership on this committee and for working so closely with me
over the years.
Today's hearing is on the important subject of blood
cancers: leukemia, lymphoma, and multiple myeloma.
Seeing everyone gathered here this morning and the 300 out
in the hall reminds me how far we have come since the days when
people were afraid to even say the word ``cancer.'' Today we
are not only discussing these diseases openly, but we are
celebrating some remarkable advances in fighting them.
Just last month, the FDA approved what is perhaps the most
promising cancer drug ever developed. This drug called Gleevec
was given to 54 patients with chronic myeloid leukemia. In 53
of those patients, the disease basically disappeared. A year
later, 51 had a normal blood count.
One reason this is so exciting is it is the first FDA-
approved drug that directly turns off the signal of a protein
known to cause cancer. Many researchers believe it marks a new
era in the war against this disease.
We are also learning more about the use of thalidomide in
treating multiple myeloma. Those of us who remember the
devastating birth defects caused by thalidomide in the 1950's
might find it hard to believe that the drug could stave off
cancer, but that does seem to be the case.
Much work remains to be done. That is one reason why the
members of this subcommittee are fighting so hard to raise the
funding for the NIH, to find better treatments and cures for
diseases like leukemia, lymphoma, and multiple myeloma.
We are fortunate to have a distinguished panel of guests
with us this morning to discuss blood cancers. I would like to
personally extend a special welcome to Dr. Sandra Horning,
Professor of Medicine at Stanford University School of
Medicine. Dr. Horning is a native of Creston, Iowa, right in my
back yard, and she earned her B.A. and M.D. from the University
of Iowa. So, I am particularly proud of the work that she is
doing on lymphoma.
I also want to thank Geraldine Ferraro, a long-time friend
and coworker of mine in the House of Representatives, a leader
in my party, and I think a leader for a lot of us throughout
the Nation. I want to thank her for being here this morning.
Ms. Ferraro has been a trailblazer her whole life; first, of
course, in Government and politics, and now as an advocate for
medical research. All of us were saddened to learn about her
multiple myeloma, but we are grateful that she has decided to
speak out about her experiences.
I want to recognize some other Iowans who are here today:
Scott Smith of WOI TV, Catherine Rhoda, a patient advocate, and
her husband John, Dr. George Weiner, a researcher at the
University of Iowa. And I want to thank all of you for making
the trip to Washington to be with us this morning.
STATEMENT OF RICHARD KLAUSNER, M.D., DIRECTOR, NATIONAL
CANCER INSTITUTE, NATIONAL INSTITUTES OF
HEALTH, DEPARTMENT OF HEALTH AND HUMAN
SERVICES
Senator Harkin. We will first start off with a long-time
friend and a great leader in our battle against cancer. Dr.
Richard Klausner was appointed Director for the NCI in 1995.
Previously he served as Chief of the Cell Biology and
Metabolism Branch of the National Institute of Child Health and
Human Development. He began his career at NIH in 1979 after
post-graduate work at Harvard. He received his undergraduate
degree from Yale and his medical degree from Duke University.
Dr. Klausner, I personally want to thank you for your
tremendous leadership at the National Cancer Institute and for
all of your willingness to keep us briefed and up to date on
everything. Welcome again this morning, and please proceed.
Dr. Klausner. Thank you, Mr. Chairman. I want to thank you
and the committee for holding this hearing on leukemia,
lymphoma, and myeloma. These are a very complex and extremely
diverse set of dozens of different diseases whose overall
burden is immense. Currently there are about 700,000 Americans
alive who have received the diagnosis of one of the three
classes of diseases. One hundred thousand new cases will be
diagnosed this year, and 60,000 Americans will succumb to one
of these diseases this year.
These diseases have long been at the forefront of oncology,
or cancer research, in terms of basic science, clinical
research and application, and progress in these diseases
mirrors the ups and downs, the highs and lows of the history of
cancer research. For some diseases, we can now achieve 80 to 90
percent cure rates whereas, in others, the ability to effect
cure is rare.
What I want to do briefly this morning is show you some of
the directions where we are going, as you and I have talked
about quite a lot over the last 5 or 6 years. But before I do
that, let me just describe a little bit of what these diseases
are. As you said, these are diseases of the cells that make up
the immune and the blood systems.
All of these cells arise from a multi-potential stem cell
that goes through a very complex, specific pattern of changing,
of development, to differentiating so that they become the
dozens of specialized cells of the immune and blood systems.
This is important because each different disease is defined
by two things: one, what type of specialized cell this cancer
arises in; and two, the type of DNA or genetic alteration that
results in that type of cell going from a normal cell to a
cancer cell.
Now, critical to the theme of how we are going to approach
successful prevention and treatment of these diseases, for all
cancers, is to understand their causes and to better define
them. I have some posters here to illustrate. These diseases
really are many different diseases. Often we misclassify these
diseases by giving them the same name. This is a problem. We
need to be able to move to precise and definitive ways of
defining and diagnosing each cancer, knowing what is wrong in
each of them, and then targeting our therapy to what is wrong.
Let me show you one example in lymphoma. I know this may be
a little hard to read, but there is one particular type of
lymphoma called diffuse large cell lymphoma. We have developed
therapies, combination chemotherapy, that will cure about 45
percent of patients. The question is why 45 percent? One
possibility is that this is not one disease. And as I have
presented to this committee before, advances in technology,
genomics, and molecular biology have allowed us to rethink our
fundamental approach to classification of these diseases.
On this first poster is some very new information that
shows when we use a new technology called DNA chips, which we
have talked about before, this single disease, a disease that
we had a single name for just a year ago, is at least two
diseases. Perhaps most strikingly, when we now look at the
ability to cure patients with these two diseases, we can see
that one type of disease can be cured over 80 percent of the
time and the other type of disease can rarely be cured. This is
the type of change in our approach that is going to guide how
we are going to develop new therapies.
Now let me briefly run through a few of these new therapies
and a few of our new approaches.
NEW THERAPIES
Senator Harkin described this new drug Gleevec that targets
the molecular machine responsible for a particular form or
leukemia, chronic myelogenous leukemia. It is also present in
some other cancers. This is a drug that stops or shuts off the
molecular machine that causes this cancer. As Senator Harkin
said, over 90 percent of patients with CML treated with this
single oral drug have gone into complete and sustained
remission.
On the next poster we can see an example of targeting the
immune system itself against some of these diseases. This
represents a study being done in Bethesda at the National
Cancer Institute that has found a particular molecular target
that is present on particular forms of leukemia, in this case a
type of leukemia called hairy cell leukemia. This has led to
the creation of a new molecular drug that has the specificity
of an antibody and which is linked to a very toxic compound
from a bacteria. This toxin, a single molecule of which gets
into a cell, is sufficient to kill the cell, and this is now
being used against hairy cell leukemia. In the original
results, in patients for whom all other treatments had failed,
over 90 percent have gone into complete and sustained
remission.
The next example is another immunologic approach where we
are learning how to actually raise vaccines to vaccinate an
individual against their own cancer. This looks particularly
promising in these sorts of malignancies. In this case, in a
trial headed again by an NCI investigator, Dr. Kwak, looking at
a type of lymphoma for which we have no definitive treatment,
what he has seen is about 85 percent of patients in whom an
immune response can be raised against their cancers go into
complete and sustained remission, something we have never seen
before. This remission is not only a complete clinical
remission, but we cannot even detect with our most sensitive
molecular measures that any of the disease is there.
As we heard before, myeloma has been an extremely difficult
disease to make progress against. But recently an old drug,
thalidomide, an infamous drug from a generation ago, was
recognized to inhibit blood vessel formation, and in fact, this
is the first drug that is showing some significant and
encouraging responses in about 30 percent of patients with
myeloma. There is a lot more to do.
Let me just finish by describing how we are going about
making sure that we make the right decisions about what to do.
PREPARED STATEMENT
We recently finished a 9-month process with the leukemia,
lymphoma, and myeloma community, including researchers,
clinicians, patients, and advocacy groups, to create a
strategic plan outlining what we need to do, what we need to
know, what barriers we need to overcome to create a more
definitive and successful research program against these
diseases. This is called a PRG, or Progress Review Group. It
has been a marvelous partnership among the entire community. We
have now received this report, and over the next year will be
working with the community to very aggressively implement the
many recommendations. There is an enormous amount to be done,
but I think there are few areas of cancer where the progress in
science has as much possibility for rapid application than in
this diverse set of diseases.
So, I appreciate your attention to these diseases and for
having this hearing.
[The statement follows:]
Prepared Statement of Richard Klausner
Good morning. I am Richard Klausner, M.D., Director of the National
Cancer Institute. Thank you, Chairman Harkin, Senator Specter, and
distinguished Members of the Subcommittee for inviting me to speak with
you about research on hematologic cancers.
Despite advances in diagnosis and treatment and improvements in
patient survival, hematologic cancers continue to have a significant
impact on the lives of Americans. Right now, almost 700,000 Americans
are living with leukemia, lymphoma, or myeloma (LLM), and an estimated
100,000 new cases occur each year. Although mortality has declined and
5-year survival rates have increased among adults and children with
certain forms of these diseases, an estimated 60,000 Americans will die
of them in 2001. For all forms of leukemia, the five-year survival rate
is only 46 percent, for non-Hodgkin's lymphoma it is 54.2 percent, and
for multiple myeloma it is only 28 percent. Despite the significant
decline in the death rate for children with leukemia, this disease
still causes more deaths in children in the United States than any
other disease. Furthermore, the death rates for non-Hodgkin's lymphoma
and multiple myeloma are increasing at a time when death rates for
other cancers are dropping. Since the 1970's, incidence rates for non-
Hodgkin's lymphoma have nearly doubled, although during the 1990's the
rate of increase appeared to slow. Hematologic cancers strike
individuals of all ages, from children to the elderly; men and women;
and all races.
WHAT ARE LEUKEMIA, LYMPHOMA, AND MULTIPLE MYELOMA?
To understand these diseases, we must first understand the normal
development of the cells they affect. Hematopoiesis is the process by
which blood cells form and mature. All the different types of blood
cells arise in the bone marrow from a common pluripotent hematopoietic
stem cell, and undergo a series of developmental steps to differentiate
into mature cells and assume specific roles in the body. New, immature
blood cells may stay in the marrow to mature or may travel to other
parts of the body to mature. Normally, blood cells are produced in an
orderly, controlled way, as the body needs them. Some circulate
throughout our bodies via blood vessels and lymph vessels. Some reside
in the lymphatic tissues that are primarily concentrated in lymph
nodes, thymus, spleen, and in most of our major organ systems.
Leukemia, lymphoma, and multiple myeloma are all cancers of the
blood-forming organs, or hematopoietic neoplasms. They arise due to
errors in the genetic information of an immature blood cell. As a
consequence of these errors, the cell's development is arrested so that
it does not mature further, but is instead replicated over and over
again, resulting in a proliferation of abnormal blood cells. Nearly
every stage of the hematopoietic process can give rise to a distinct
type of cancer.
Historically, scientists and physicians have classified these
diseases by their locations in the body, the appearance of affected
cells under the microscope, and the natural progression of the
diseases. In leukemia, the cancerous cells are discovered circulating
in the blood and bone marrow, while in lymphoma, the cells tend to
aggregate and form masses, or tumors, in lymphatic tissues. Myeloma is
a tumor of the bone marrow, and involves a specific subset of white
blood cells that produce a distinctive protein.
Leukemia can arise in either of two main groups of white blood cell
types--lymphocytes or myelocytes. Either type of leukemia can be acute,
a rapidly progressing form of the disease in which the affected cells
are very immature and unable to serve their proper purpose, or chronic,
which progresses more slowly and is distinguished by cells that are
relatively well differentiated but still function poorly. Lymphoma
involves lymphocytes and can also be subclassified. Non-Hodgkin's
lymphoma (NHL) is the more prevalent form of the disease. Among non-
Hodgkin's lymphomas, indolent disease progresses slowly and exhibits
well-differentiated lymphocytes, while the more aggressive forms are
characterized by lymphocytes with far less differentiation. Hodgkin's
disease, which is less common than NHL and has different clinical and
epidemiological features, has historically been distinguished from NHL
by the presence of distinctive cells called Reed-Sternberg cells.
Leukemias, lymphomas, and myelomas share some common features, but
there are major differences among them--and there are similarities and
differences within each disease group. These cancers actually represent
a large number of diseases that vary significantly in their causes,
molecular profiles, and natural progression. In the past decade we have
a experienced a revolution in the field of molecular biology that has
brought new tools that are helping us refine cancer classification in
terms of the molecular changes that distinguish a normal cell from a
cancerous one, and draw differences between cancerous cells of
different types.
This is an area of research rich in scientific promise, and the NCI
has issued the Director's Challenge: Toward a Molecular Classification
of Tumors, in which investigators are creating comprehensive molecular
profiles of tumors using DNA, RNA, or protein-based technologies. These
profiles will be used to define more informative, and clinically
predictive, molecular classification schemes for human cancers.
MOVING TOWARD A NEW UNDERSTANDING OF LLM
A major NCI initiative, the Cancer Genome Anatomy Project (CGAP),
has resulted in the cataloging of tens of thousands of human and mouse
genes. The CGAP database is a unique resource that allows scientists to
develop tools to perform large-scale genomic analyses to characterize
tumors genetically. This genetic characterization can help explain why
patients diagnosed with the same cancer differ dramatically in their
responses to treatment. For example, a collaboration of scientists
(including NCI scientists) genetically analyzed diffuse large B-cell
lymphoma, an aggressive cancer that is the most common type of non-
Hodgkin's lymphoma. For 40 percent of patients with this diagnosis,
standard multi-agent chemotherapy is curative. A compelling clinical
problem is to understand why the remaining 60 percent of patients
succumb to this disease despite chemotherapy. Reasoning that the
varying therapeutic responses of patients with diffuse large B-cell
lymphoma are due to undefined molecular differences in their tumors,
researchers used DNA microarray technology to define the gene
expression profiles of diffuse large B-cell lymphoma samples on a
genomic scale. This new technology is capable of measuring the activity
of tens of thousands of genes at the same time, thus creating a
molecular portrait of the cells being studied.
For this study, the CGAP was used to create a specialized DNA
microarray, the Lymphochip, which is enriched in genes that function in
normal and malignant lymphocytes. Lymphochip microarray analysis of
gene expression in diffuse large B-cell lymphoma samples revealed that
this single diagnosis actually combines two distinct diseases that
differ in the expression of hundreds of genes. The two types of diffuse
large B-cell lymphoma that were discovered each resemble a different
type of normal B lymphocyte, suggesting that these cancers have
distinct cellular origins. Clinically, patients with these two types of
diffuse large B-cell lymphoma had strikingly different responses to
chemotherapy. Patients with one lymphoma subtype, termed germinal
center B-like diffuse large B-cell lymphoma, had a favorable prognosis:
75 percent of these patients were cured by chemotherapy. Patients with
the other lymphoma subtype, termed activated B-like diffuse large B-
cell lymphoma, had a poor response to chemotherapy with less than one
quarter of these patients achieving a long-term remission. This study
provides a clear demonstration that genomic-scale gene expression
analysis can define clinically important subtypes of human cancer.
This powerful new technology is now being used to study many
different types of cancers, including leukemia and multiple myeloma, in
an attempt to identify disease subgroups. For example, a new project,
``Molecular Taxonomy of Pediatric and Adult Acute Leukemia,'' will
attempt to correlate the expression pattern of over 30,000 genes with
treatment outcome and with cytogenetic abnormalities for both acute
lymphocytic leukemia and acute myeloid leukemia. In the future, such
gene expression profiling of cancer cells will be used to guide
patients towards therapies that are tailored for their particular
diseases.
CAUSES, RISK FACTORS, AND EPIDEMIOLOGY OF LLM
Our understanding of the causes of these diseases is extremely
limited, perhaps in part due to extreme heterogeneity of the diseases
and the inadequacy of the traditional classification schemes to
adequately address this heterogeneity. As our knowledge base about
molecular subtypes grows, we hope that we will be better able to
understand the relationships between causative factors and the
development of LLM.
Leukemia
The leukemias are very heterogeneous, with patterns of occurrence
differing by age, sex, and racial and ethnic group. For example,
highest incidence of acute lymphoblastic leukemia (ALL) is in children,
ages 2-4, while chronic lymphocytic leukemia (CLL) is rare before age
30, and has the highest incidence among the elderly. Chronic myeloid
leukemia (CML) has a higher incidence among African-Americans than
Caucasians, while the incidence of CLL is highest among Caucasians and
extremely rare in Asians.
The causes of leukemia in children and adults are largely unknown,
but increased or decreased risks for developing leukemia have been
associated with several factors. In an ongoing, collaborative follow-up
study with Japanese investigators, NCI scientists have found strong
evidence of radiation-induced risks for the acute leukemias and CML
among Japanese atomic bomb survivors. NCI investigators and others have
shown that radiotherapy and chemotherapy for a wide variety of diseases
have been linked with moderately increased risks of acute myeloid
leukemia (AML), although the benefits of treatment far outweigh the
risks.
Occupational exposures to ionizing radiation and certain chemicals
such as benzene have also been linked with increased risk of acute
leukemia. NCI is conducting an epidemiologic study of workers in China
exposed to benzene at levels lower than previously studied, to
characterize leukemia rates and to determine mechanisms of action and
factors affecting carcinogenicity of benzene. In addition, cigarette
smoking has been associated with modest increases in acute leukemia but
the evidence is not yet conclusive.
The first known human retrovirus, T-lymphotropic virus type 1
(HTLV-1), discovered at NCI in 1981, is the primary cause of adult
leukemia and lymphoma arising from lymphocytes known as T cells.
Certain genetic conditions can increase the risk for acute leukemia,
including Li-Fraumeni syndrome, Down's syndrome, Bloom's syndrome and
several other rare conditions.
Lymphoma
NCI investigators have recently reported on investigations of
lymphoma incidence trends. Over the last ten years, researchers have
studied the histologic types of lymphoma that are on the rise;
illnesses, including other cancers, associated with lymphoma;
occupational groups that may be at increased risks; and the role of
genetic susceptibility. Recent research has identified several possible
candidates for increasing risk including pesticides, organochlorine
compounds, solvents, drinking water nitrates, and hair dyes. We are now
evaluating whether these common exposures are contributing to the rise
in NHL among some populations and investigating other hypothesized risk
factors such as infectious agents, medical conditions, medical
treatments, and genetic factors.
There has been considerable research on the association between
infectious agents and cancer. Helicobacter pylori is a bacterium
associated with a particular rare type of lymphoma, mucosa-associated
lymphoid tissue (MALT) lymphoma that arises in the stomach. Both
Hodgkin's disease and non-Hodgkin's lymphoma, particularly some of the
more aggressive forms, occur with increased frequency among adults and
children infected with the human immunodeficiency virus (HIV), the
virus that causes AIDS. In HIV-infected patients, about one-half of all
lymphomas involving a type of lymphocytes called B cells are associated
with the Epstein-Barr virus, including virtually all primary central
nervous system lymphomas in patients with AIDS. A new Program
Announcement, in collaboration with National Institute for Dental and
Craniofacial Research, is being issued to stimulate research on viruses
associated with the development of lymphomas among persons who are
infected with HIV. The AIDS-Cancer Cohort is studying men infected with
HIV to examine interactions with various environmental exposures that
may contribute to the excess risk of lymphoma. Information from this
project may be of value beyond the setting of HIV, as it may yield more
fundamental biologic understanding of the interplay of viruses and
chemicals in the development of lymphoma. A rare type of lymphoma,
called Primary Effusion Lymphoma, which arises in the lining of the
lung, heart or abdomen, is tightly linked to, and probably caused by,
the Kaposi's sarcoma herpes virus (KSHV). People who have both HIV and
KSHV are at particularly high risk. Because viruses similar to KSHV are
known to cause lymphoma in animals, efforts are in progress to identify
new, lymphoma-related viruses in people.
NCI scientists are conducting very large epidemiologic studies
addressing the relationship between the environment and lymphoma
development. In a population-based case-control study of non-Hodgkin's
lymphoma, NCI investigators, collaborating with the Centers for Disease
Control and Prevention (CDC), assessed exposures to pesticides,
solvents, and other factors using computer-assisted personal
interviews, residential carpet dust samples, drinking water samples,
and blood samples. Analysis continues, as investigators extract DNA
from blood or saliva samples to assess the interaction between genetic
variations and environmental risk factors.
The Agricultural Health Study (AHS) is following 90,000 healthy
farmers and their family members in Iowa and North Carolina in an
effort to measure their risks of developing lymphoma and leukemia. NCI
and National Institute of Environmental Health Sciences launched the
AHS in 1993 after previous NCI research implicated occupational
exposures to pesticides in the development of lymphoma. The study
assesses the risks of other cancers and diseases, as well.
A new initiative called Interlymph, coordinated by NCI and
involving investigators in Europe and Australia, features a pooled and
simultaneous analysis of thirteen case-control epidemiologic studies of
non-Hodgkin's lymphoma. The international consortium of collaborators
will examine pathology, infectious agents, family history data, genetic
factors, and methodologies needed to accurately assess possible links
with the development of lymphoma.
Multiple Myeloma
The median age for diagnosis of multiple myeloma is 71 years of
age. The incidence of multiple myeloma is much higher in blacks than
whites, and is higher among males. Similar to incidence rates, the
death rates are higher among males than females and higher among blacks
than whites. This is one of the few cancer sites in which the survival
rate is higher for blacks than for whites. The causes of multiple
myeloma and the reasons for the racial disparity in incidence are
unclear.
Some studies have suggested the role of ionizing radiation, certain
organic solvents and chemicals, as well as employment in farming and
agricultural occupations. In recent studies, genetic factors, low
socioeconomic status (SES), and obesity have been implicated. Recent
attention has also focused on viruses and other infectious agents, but
their role in the etiology of myeloma remains unclear. There is growing
evidence that certain cytokines and chromosomal abnormalities may be
involved in the pathogenesis of multiple myeloma. These laboratory-
based genetic measures need to be incorporated into future
epidemiologic studies to better understand the complex relationships
between genetic and environmental factors in the development of this
disease.
In a recent study, NCI investigators found that low SES, whether
measured by occupation-based SES, income, or education, may account for
about half of the excess incidence observed among blacks. Low SES may
be a surrogate for a set of negative environmental characteristics,
such as poor housing, dangerous jobs, lack of access to medical care,
poor nutrition, and exposure to infectious agents, all of which may
have a role in this disease.
The rarity of this cancer makes it difficult to adequately
investigate in a single study, so that collaborative efforts involving
a variety of hematopoietic malignancies are being pursued.
NEW STRATEGIES FOR TREATMENT OF LLM
Therapeutic research in the treatment of patients with hematologic
malignancies has made enormous progress over the past 50 years, and the
NCI has shepherded this important work. Many years ago, NCI established
the National Service Center to enable basic scientists to design and
test chemical agents for evidence of anti-tumor activity. In addition
to pioneering cancer drug screening, the NCI funded an entire
preclinical drug discovery and development program. The NCI has
continuously supported investigators to pursue all phases of clinical
evaluation of products emanating from their own discovery and
developmental efforts, and interacts with the pharmaceutical industry
and academic institutions to explore their novel agents.
In the last decade, there has been an enormous investment in
defining molecularly targeted agents in cancer chemotherapy. Recently
we have seen some inspiring success stories, all of them direct results
of this new approach. The first evidence of a consistent gene mutation
associated with a particular cancer was provided about 40 years ago by
the recognition of the Philadelphia chromosome, an abnormally small
chromosome 22, in chronic myeloid leukemia (CML). Some years later,
researchers noted that while chromosome 22 was shortened, chromosome 9
was lengthened in CML patients, which suggested that the pieces of each
chromosome were exchanged, or translocated. This observation was
followed by the identification of a unique fusion gene, called bcr-abl,
resulting from the translocation, and the eventual development 5 years
ago of one of the first oncogene-targeted drugs, STI571 or Gleevec.
This compound, which was recently approved by the United States Food
and Drug Administration (FDA), is directed at the bcr-abl gene product,
which is expressed in about 95 percent of CML patients, and in some
patients with other types of cancers. Gleevec has shown remarkable
promise in the treatment of chronic-phase CML, and NCI is partnering
with Novartis, the drug manufacturer, to facilitate a profusion of
clinical trials evaluating Gleevec in other cancers, including
Philadelphia chromosome-positive ALL in adults and children. Additional
trials are assessing the potential benefits of combining Gleevec with
other chemotherapeutic agents. Molecular analyses of other types of
leukemia have now produced the identification of more than 100
additional oncogene targets that may be accessible to similar drug
development strategies.
Monoclonal antibodies are showing great promise in the treatment
LLM. Among them, Rituximab, which was originally approved by the FDA in
1997 for the treatment of non-Hodgkin's lymphoma (NHL), is an antibody
directed at a cell surface antigen expressed on B lymphocytes and has
been shown to be effective against many types of B cell malignancies.
Currently, for both children and adults, rituximab is under study in
combination with other therapies, including other monoclonal
antibodies, attempting to attack multiple targets on a single cell
type.
In addition, NCI-sponsored studies are evaluating several new
antibodies. Generally, leukemias, lymphomas, and multiple myelomas are
derived from cells of the immune system and therefore frequently
express antigens that are present on normal immune cells such as B-
cells or T-cells. Since these proteins are not present on other human
cells and are not present on the stem cells that give rise to normal B-
cells and the T-cells, the antigens are excellent targets for cancer
therapy. NCI researchers have devised a cancer treatment strategy that
kills cells containing B-cell or T-cell specific antigens. When this
occurs the normal cells are regenerated, but the cancer cells are not.
One strategy is to fuse the portions of antibodies that bind to CD22 (a
B-cell antigen) or CD25 (a T-cell antigen) to a potent bacterial toxin
termed Pseudomonas exotoxin A. The genetically modified toxin then
specifically binds to and kills cells expressing CD22 or CD25. Since
many lymphomas and leukemias express CD22 or CD25, these tumor cells
are killed.
A promising ongoing NCI study is using this approach to combat B-
cell malignancies. The antigen CD22 is expressed on about 70 percent of
lymphomas and leukemias. A recombinant immunotoxin termed BL22 has been
designed and produced to kill tumor cells expressing CD22, and patients
with hairy cell leukemia, chronic lymphocytic leukemia (CLL), and some
lymphomas have been treated in a Phase I trial. Remarkable anti-tumor
activity has been observed in patients with hairy cell leukemia.
Several patients with CLL have responded as well. Enrollment into this
trial is continuing, and once the maximum tolerated dose is
established, Phase II trials in hairy cell leukemia, CLL, and lymphomas
(in a post-transplant setting) will be opened for enrollment.
Other antibodies under investigation are coupled to other potent
anti-tumor substances, like radioactive molecules or anti-tumor
antibiotics, and have the potential advantage of being able to deliver
this tumor killing substance directly to the tumor site, where they
attack antigen-positive tumor cells that other therapeutic agents might
not penetrate well.
Anti-cancer vaccines are a high priority research area for NCI.
Unlike conventional vaccines, which are used to prevent illness, the
anti-cancer vaccines represent a therapeutic approach, which seeks to
strengthen the body's natural defenses against diseases, such as
cancer, that have already developed. Vaccine therapy for lymphomas has
shown considerable promise. Results of a recently completed lymphoma
vaccine study conducted by NCI researchers have shown that there is a
clear anti-tumor effect in a small group of patients who were
vaccinated over the course of five years. On the basis of these
promising results, NCI has launched a large-scale, multi-institutional,
randomized, phase III clinical trial, to definitively test the
experimental vaccine, which is custom-made from patients' own tumors.
Immunotherapeutic approaches for treatment of multiple myeloma are
also being evaluated. Investigators are examining the potential for
immunization strategies in which a normal donor is vaccinated with the
myeloma protein. The normal donor forms antibodies, called idiotype
antibodies, and these are used to treat the patient. Preclinical
studies of idiotype immunization demonstrate that this approach can
induce an immune response that prevents tumor relapse or progression in
myeloma models. Additional studies are determining the feasibility of
inducing an active immune response against myeloma-specific antigens,
such as MUC-1 and DF3.
The NCI is involved in the development of a large number of new
therapeutic agents with a wide array of unique mechanisms of action. We
now know that cancer arises from the disruption of fundamental cell
processes. Basic research findings have identified a plethora of
potential therapeutic targets for further exploitation. There is an
ever-lengthening list of promising agents that affect cell cycle
regulation, gene expression, apoptosis (programmed cell death), and
other cell functions, currently undergoing or awaiting investigation in
clinical trials.
A striking example of the benefit of this kind of molecularly
targeted therapy is all-trans retinoic acid (ATRA) for the treatment of
acute promyelocytic leukemia (APL). ATRA works essentially by reversing
the effects of a specific chromosomal translocation that disables both
differentiation and apoptotic processes in affected cells. The
introduction of this agent has increased the cure rate for APL from 40
percent to over 70 percent in just 10 years. Some patients who have
been treated successfully with ATRA experience relapse, and recently,
arsenicals, a group of rediscovered compounds that induce apoptosis via
a different, more broadly applicable mechanism, have shown great
utility as a second line of defense against APL. Arsenic trioxide is
now being evaluated for use in a variety of lymphoid malignancies, as
well as other cancers, and for use in childhood APL, and also for use
as a first line treatment.
Finding effective treatments for multiple myeloma has proven
extremely challenging for cancer researchers. Recently, the success of
thalidomide in treating MM patients has been very encouraging.
Thalidomide effectively arrests tumor growth by stimulating anti-tumor
immune response, interfering with communication between tumor cells and
the surrounding tissue, and inhibiting the growth of new blood vessels
(angiogenesis) near the tumor. Thalidomide's anti-angiogenic activity,
was first recognized as the feature that caused birth defects in the
children of women who took thalidomide in the 1950's and 1960's. Astute
researchers theorized that the same feature could prove useful in
restricting the blood supply to tumors. NCI-sponsored investigators
recently report a 30 percent response rate for MM patients receiving
thalidomide on a clinical trial. New trials are seeking to optimize the
role of this agent, and some other antiangiogenic agents are being
evaluated, as well. Because anti-angiogenic drugs have the potential to
cause defects in a developing fetus, pregnant woman are excluded from
participating in clinical research on these drugs.
Bone marrow transplantation and peripheral blood stem cell
transplantation techniques continue to be tested in clinical trials for
certain LLM patients. Sometimes cancers become resistant to treatment
with radiation therapy or chemotherapy. Very high doses of chemotherapy
may then be used to treat the cancer. Because the high doses of
chemotherapy can destroy the bone marrow, marrow is taken from the
bones before treatment. The marrow is then frozen, and the patient is
given high-dose chemotherapy with or without radiation therapy to treat
the cancer. The marrow is then thawed and given back to the patient to
replace the marrow that was destroyed. This type of transplant is
called an autologous transplant. If the marrow is taken from another
person, the transplant is called an allogeneic transplant. Another type
of autologous transplant is called a peripheral blood stem cell
transplant. The patient's circulating stem cells are collected, treated
with drugs to kill any cancer cells, then frozen until they are
returned to the patient. This procedure may be done alone or with an
autologous bone marrow transplant.
The role of stem cell transplantation in caring for patients with
LLM varies with tumor type. Autologous stem cell transplantation
clearly benefits patients in a chemotherapy-sensitive relapse of their
disease, but its role as initial treatment is undefined. A national
trial is comparing the efficacy of initial transplantation with
transplantation at the time of first relapse. Other studies are
evaluating the role of biological therapies such as interleukin-2, and
immune response stimulator, and rituximab for their effectiveness in
enhancing the benefit of transplantation.
Many patients do not benefit from stem cell transplantation, and
major efforts are directed at identifying the reasons and to develop
methods to improve on these results. Some investigators are developing
methods to harness patients' own immune responses. Alternatively, other
researchers are using a technique called donor leukocyte infusion (DLI)
that introduces T cells capable of generating a graft-versus-tumor
effect (in which the donor cells attack the patient's cancerous cells).
However, they are also capable of generating a potent graft-versus-host
disease (GVHD, in which the donor cells attack the healthy tissues of
the patient) that could be fatal to the patient. Studies of the array
of T cells that are present post DLI are being conducted to better
understand which T cell populations are necessary to achieve the
desired result while minimizing GVHD.
Allogeneic bone marrow transplant may cure patients who do not
respond to standard chemotherapy, but the mortality of this procedure
in patients with LLM has been very high. Moreover, age restrictions
limit the number of patients who might be eligible for this procedure.
There has now been an expanded information base on the use, for non-
Hodgkin's lymphoma, of non-myeloablative transplants (in which the bone
marrow is not completely destroyed) with DLI. Recently, investigators
have described their experience with patients over the age of 55 years.
GVHD occurred less frequently than expected and many patients were able
to go through the procedure without requiring hospitalization. As a
consequence, the notion that more intensive treatment is better is
being challenged, and the role of the immune system in cancer
progression is being better delineated.
The NCI sponsors the International Bone Marrow Transplant Registry,
which is the world's largest body of data on outcomes following
transplantation for LLM and other cancers. Data are provided from more
than 400 centers and there are now data for more than 65,000
transplants worldwide. The information collected is used for
determining transplant regimens for specific clinical situations,
identifying prognostic factors, comparing transplant regimens,
comparing transplant with non-transplant approaches, evaluating cost
and cost-effectiveness, planning clinical trials, and developing
approaches to evaluate outcomes.
Clinical trials for LLM treatment have demonstrated remarkable
success and are a vital component of the NCI's research program.
Currently, our clinical trials database contains descriptions of 177
NCI-sponsored leukemia treatment trials, 170 for lymphoma, and 67 for
multiple myeloma. Our clinical trials program is the place where
promising new strategies discovered at the laboratory bench are applied
to real human problems at the bedside. Clinical trials offer cancer
patients access to state-of-the-art care, and provide us the
opportunity to learn something from every patient that may help someone
else. Our rapid pace of discovery in the basic biology of cancer is
refining our knowledge of how to intervene in cancer development, and
clinical trials are the crucial final step in bringing these
discoveries to people who are battling cancer.
CONCLUSION
Progress in our understanding of cancer and our ability to detect
and treat it have led to a real and continuing decline in the cancer
incidence and death rates. However, our excitement over important
scientific progress and the very real human gains that result is
tempered by the knowledge that far too many Americans continue to
suffer and die from cancer each day. Moreover, all groups of people are
not benefiting equally from our advances against cancer. NCI is
embracing the challenge of understanding the causes of health
disparities in cancer and developing effective interventions to reduce
them. Plans call for increasing fundamental research into the social
causes of health disparities, the psychosocial factors that mediate
them, and the biologic pathways that can explain their impact. In
addition, we will expand our cancer control intervention and population
research on disparities, better define and monitor cancer-related
health disparities, and strengthen training and education in this
research area. Effective communication empowers people to make informed
cancer-related decisions and to engage in behaviors that will improve
their health. Few other initiatives have the potential to
simultaneously improve health outcomes, decrease health care costs, and
enhance community satisfaction. Our intent is to learn how to help
people distinguish important from insignificant health risks and deal
with contradictory or inaccurate health messages so they can make
informed choices.
Too many Americans, for a host of reasons, lack access to high
quality, cutting-edge cancer treatment and care. NCI is launching
research to improve the quality of cancer care by strengthening the
information base for cancer care decision making. Researchers seek to
better understand what constitutes quality cancer care, with an
emphasis on the patient's perspective; identify geographic, racial/
ethnic, and other disparities in who receives quality care; and
strengthen the scientific basis for selecting appropriate
interventions. Our goal is to enhance the state of the science for
defining, monitoring, and improving the quality of cancer care and
inform Federal decision making on cancer care delivery, coverage, and
regulation.
We have learned the value of including as broad a constituency as
possible in our review, advisory, and planning activities, and we have
forged new relationships with patients, practitioners, scientists in
different fields of research and medicine, other government agencies,
private sector companies, innovators in technology, and many other
partners where such alliances were rare or non-existent only a few
years ago. Illustrating our commitment to this philosophy as we seek to
accelerate progress against LLM, the NCI convened a Progress Review
Group (PRG) last year to conduct an intensive review of our research
portfolio in LLM. This initiative, one of a highly beneficial series of
PRG's fitting within NCI's new disease-specific planning framework,
featured expert panels who provided a comprehensive view of the state
of our current knowledge, and you will see that many of our research
priorities will reflect the recommendations the PRG described in their
report, issued last month, and available on our website at: http://
osp.nci.nih.gov/prg__assess/prg/llmprg/llm__rpt.htm.
We have a special interest in enlisting the help of cancer
survivors. The NCI created the Consumer Advocates in Research and
Related Activities (CARRA) program to encourage people affected by
cancer to provide their viewpoint and ideas directly to NCI staff so
that the NCI can incorporate this perspective into our programs and
activities. Our goal is to recruit 150 consumer advocates (cancer
survivors, family members, or those who are involved in cancer-related
activities like support groups, cancer hot lines, or advocacy groups)
to become members of CARRA and represent many different cancer types,
age groups, and ethnic groups from across the Nation. In addition to
participating in NCI activities, CARRA members will represent the
opinions of their groups and play critical roles as two-way information
links between their own communities and constituencies and the NCI.
NCI has been entrusted with guiding our Nation's commitment to a
complete understanding of cancer: from understanding how a normal cell
becomes cancerous to understanding why some people get cancer and
others do not; and across the continuum through detection, diagnosis,
treatment, survivorship, and ultimately prevention. NCI's mission is
broad and our approach is necessarily ambitious, because, while our
primary role and our expertise is research, our interest is people: our
families, friends, neighbors, and colleagues--and yours. Our goal is to
eradicate cancer and save the lives of those who would otherwise be
lost to us.
Thank you, Mr. Chairman, for giving me this opportunity to share
with you our progress against hematologic cancers. I will be pleased to
answer any questions you may have.
STATEMENT OF SENATOR ARLEN SPECTER
Senator Specter [presiding]. Well, thank you very much, Dr.
Klausner for your lucid testimony, as usual.
First, I want to acknowledge the generous comments made by
Senator Harkin who noted his chairmanship of this subcommittee
from 1989 through 1994, and mine from 1995 through a few days
ago. We have worked really for a common purpose. I learned a
long time ago if you want to get something done in Washington,
you have to cross party lines, and so far as this
subcommittee's activities, I think it makes little, if any,
difference as to who has the gavel.
We have pursued funding for NIH in a very vigorous way, as
everyone knows. We have added more than $8 billion in increases
for the NIH and we are on a path to double funding over 5
years. This year we have targeted and increase of $3.4 billion.
Each time we have gone to the Budget Committee for more money,
we have gotten congratulations but no additional cash. We have
had to establish priorities within the subcommittee.
We have had a whole series of hearings on a variety of
special ailments, muscular dystrophy, amyotrophic lateral
sclerosis, Parkinson's, Alzheimer's, so many, many ailments. We
responded to a special request by our colleague, Senator Kay
Bailey Hutchison, whose brother suffers from myeloma, and also
made the subcommittee aware former Congresswoman, Vice
Presidential candidate Geraldine Ferraro has this ailment.
We have held these hearings because of an effort to create
public awareness as to the fact that some serious malady can
affect anyone of you or your family. We try to get public
support for research for NIH and, beyond that, research for
implementing the NIH funds. For example, on stem cell research,
you testified in this room just a few weeks ago, Dr. Klausner,
as to the impact stem cells could have on cancer. We had a
private follow-up conversation.
I regret that we do not have a bigger room. We have a line
which goes for several blocks outside, which signifies how much
public interest there is in this subject and all taxpayers
should have the opportunity to hear the testimony.
Senator Hutchison. Mr. Chairman, could I just make a
suggestion on that point? There are so many people outside,
that I wondered if after about 30 minutes, some of you might
rotate out and let them come in, just on a voluntary basis so
that everyone has a chance to see some part of the hearing.
Senator Specter. I think that is a good idea, Senator
Hutchison.
You folks in the rear can move up to the sides, and anybody
who would like to be a Senator for a hearing can take some of
these seats. You may have to leave if some more of our
colleagues come. But come on up. Come on up to the side so that
we can have the maximum number of people come in at the present
time.
I want to make one additional comment this morning that I
had not intended to make, but there is a front-page story in
the Washington Post today which I find very disquieting, and
that is about administration testimony given yesterday to a
subcommittee of the House of Representatives on the issue of
stem cells.
This is generally known. These stem cells are extracted
from embryos which are going to be thrown away. At the present
time, there is a ban on any Federal funding being used to
extract stem cells from embryos. But there is currently a
ruling by the general counsel for the Department of Health and
Human Services that once the embryos are removed, that Federal
funds can be used for stem cell research.
The administration, according to this morning's press--and
I am going to have to read the transcript and get the
statements--is making the suggestion that that is subject to
change by the President. I do not know about that. If you have
a lawyer's opinion given by the general counsel for the
Department of Health and Human Services that it is appropriate
to fund research on stem cells, once extracted, it seems to me
that is that, especially in the context where that ruling was
made some time ago, and the Congress has not changed it. There
is a presumption which attaches to a ruling of that sort where
Congress has not made a change. If Congress disagrees with
that, Congress can make a change in it.
Senator Harkin and I and others have been working very hard
on the issue to get support, even to rescind the ban on use of
Federal funds for extracting stem cells from embryos. One of
our colleagues, Senator Gordon Smith, a very strong pro-life
Republican--and many who favor use of Federal funds to extract
stem cells on the research are pro-life Republicans. But
Senator Gordon made a very valid point, that it is different if
you have an embryo in a dish as opposed to having an embryo in
a womb. If you have an embryo in a woman's womb, there is
movement toward life. If you have an embryo in a dish and so
many of them are destroyed, there is just no real reason not to
use those embryos to save lives since they are going to be
discarded.
Now, it may well be that the scope of the administration's
position is narrow enough so that it will not impact on either
of the two questions: one, use of Federal funds on the stem
cells once taken from the embryos; or on the second question,
use of Federal funds to remove stem cells from embryos.
We have been talking among Senators and it may well be that
we have more than 70 votes in the U.S. Senate to remove the ban
on using Federal funds for extracting stem cells from embryos.
Senator Lott had agreed to bring the bill up which Senator
Harkin and I and many others have introduced as a freestanding
bill, and I have talked with the new Democratic leadership and
bringing the bill up may be right around the corner. In the
meantime, we are trying to deal with the administration to see
to it they will make the ruling to allow Federal researches to
extract their own stem cells.
After I yield to Senator Hutchison, Dr. Klausner, I am
going to come back to you on the issue of stem cells as an
assist on the kinds of research and treatment you are
describing here today.
Senator Hutchison, we thank you for suggesting this hearing
and give you the floor.
STATEMENT OF SENATOR KAY BAILEY HUTCHISON
Senator Hutchison. Thank you, Mr. Chairman and ranking
member. When Senator Specter was the chairman of this
subcommittee, I did talk to him about having this hearing. When
Senator Harkin then became chairman, he agreed to continue. I
want to thank you so much for leading the way and thank Senator
Harkin for continuing his interest because this is such an
important issue, one which I think has not gotten as much of
the research and the focus as perhaps now we will be able to
do.
When I first started looking into the Federal commitment to
the deadly blood cancers, leukemia, lymphoma, and multiple
myeloma, I was really amazed to know that 11 percent of all
cancer deaths come from these blood diseases, but only 5
percent of the research funding from the National Cancer
Institute is going to find the cure to these cancers.
I talked to Dr. Klausner about that personally 2 years ago,
and he could not have been more responsive. I appreciate so
much your willingness to listen and to act on the concerns that
we had. You set up the Progress Review Group, which now is able
to review and advise the National Cancer Institute, and I
really appreciate that. I think that is a major step forward.
Nevertheless, this is now, I think, an area where we are
seeing new innovations, and, because of my personal interest in
it, I know that some of the innovations, such as thalidomide,
are coming forward. There are others. So, now I think there is
something to really invest in.
Because of that, I want to say that I am introducing a bill
today with my colleague, Senator Barbara Mikulski, that will
direct the National Cancer Institute to establish a program for
research of lymphoma, multiple myeloma, and leukemia. It will
authorize $250 million for that purpose and it will also add
$25 million for education efforts because, as you know, early
detection can save lives in any kind of cancer. We have seen
the incredible results in breast cancer of early detection
through education and awareness. I want to do that for the
blood cancers as well.
Along that line, more than anything that I could ever have
done, there are people who have been willing to step up to the
plate and say, wait a minute. I have now come in contact with
this disease. I now see how neglected it has been in the area
of research. I think what Geraldine Ferraro is doing for the
future of the research capabilities is beyond any of our
expectations, and I want to thank her for coming forward and
saying let us do something about this.
It was Geraldine Ferraro who called me several months ago
and said she wanted to make sure that we do something that will
push this issue to the forefront, which resulted in this
hearing. I went to Senator Specter and I told him of her
willingness to come forward and be helpful in the education and
awareness efforts. Thank you. What you are doing is going to
have huge benefits.
I want to also just thank one other person, Kathy Giusti,
because it was Kathy who never gave up. She is the head of the
Multiple Myeloma Research Foundation. I call her a human
hurricane. It is true. She has done so much to make this
happen. She came forward. It takes time to get these things
done, but I think the culmination of your efforts is happening
this week. I thank you for that bravery.
Dr. Ken Anderson, Geraldine Ferraro's physician, is doing
so much and is so committed from his heart to the research.
I also want to thank Dr. Kantarjian, who is a renowned
physician and researcher in the area of leukemia at the
Nation's number one cancer center, M.D. Anderson. Dr.
Kantarjian actually cut short his much deserved vacation to
testify today, and I thank him for his efforts.
Last but not least, I want to say that I would not have
really been aware of this had my brother not been willing to
step forward. I went through a bone marrow transplant. We will
be there for you. Thank you.
Senator Specter. Thank you very much.
Senator Murray, would you care to make an opening
statement?
STATEMENT OF SENATOR PATTY MURRAY
Senator Murray. Mr. Chairman, let me thank you and Senator
Harkin and Senator Hutchison for your tremendous passion on
this. I think it is shared by clearly all the people in this
room. This is really an impressive hearing to have so many
people here today. I know how difficult it has been to schedule
this hearing with all that is going on on the floor in the
Patients' Bill of Rights and all of the changes in the Senate,
but clearly this is important.
I have a number of constituents who have come here from
Washington State. I had to spend a few minutes in the hall with
them because they cannot get in the room. They have traveled
3,000 miles to be here. So, I hope at some point they do get to
get in the room and hear part of this hearing.
But I just want to thank everybody who has come because I
think your presence alone shows the impact on this country.
I too want to thank Geraldine Ferraro for her courage. I
think in the last few days the awareness of the American public
of this impact on people and their lives and the awareness that
they have of the importance of research has just grown
unbelievably large, and that is because of your courage. I just
want to tell you how much I appreciate your doing this. We are
in this fight with you, and thank you for being here today.
Mr. Chairman, I know we have a number of panels who are
coming before us. I look forward to offering our questions as
they come through. Thank you very much.
Senator Specter. Thank you very much, Senator Murray.
We still do have some more room here. We have some more
chairs. If anybody in the hall wants to come up and sit on the
floor, it is not the most gentile, but you would be a part of
the hearing. Let us make that offer to those who are outside.
We have a very large group of people outside who we regret are
not accommodated here.
Dr. Klausner, Senator Harkin, the chairman, has yielded to
me for the first round of questions. We will have 5-minute
rounds. Let me say we are going to have to move right along. We
have a lot of witnesses, and we have a markup on the
supplemental appropriation bill at 11:30 this morning. So,
everybody on this panel will be involved in that.
Dr. Klausner, I want to start with a statement which you
made which summarizes the issue of stem cells on this
particular ailment. The subcommittee had asked you for your
views on stem cells, and you wrote the following. ``Probably
the most dramatic recent advancement which arose from stem cell
research is the development of the drug Gleevec for the
treatment of chronic myelogenous leukemia, CML. The development
of this drug came as a result of the careful step-wise studies
of CML cells compared to normal cells. This drug is unique in
that it results in remissions in nearly 100 percent of patients
who take it as initial therapy, has minimal side effects, and
is a pill. Furthermore, there are data that this drug may have
even broader application.''
I want to move to an issue raised in yesterday's House
hearing which talks about cloning of embryos. Certainly we can
use existing embryos that are going to be discarded without
having the cloning of embryos. To the extent that there is a
consensus against cloning, we do not have to use that as a
reason for not using stem cell research.
The question I have for you is that apparently there was
some testimony from biomedical researchers, as the news report
says, who believe that studies on stem cells from 5-day-old
cloned human embryos offers the best chance of developing
promising new therapies for a variety of debilitating diseases.
My question to you, is there anything to that? Are the cloned
embryos which produce stem cells superior to the discarded
embryos?
Dr. Klausner. There is no scientific data that I am aware
of that compares cloned human embryos to the embryonic stem
cells that can be removed from and then grown as permanent
lines from early embryos.
Senator Specter. Among the varieties of stem cells which
are possible, adult stem cells, fetal tissue, the whole range,
I think it would be good for you to put on the record the
superiority of embryonic stem cells in scientific research such
as you have been referring to.
Dr. Klausner. Yes. We have that information from the mouse
where we have been able to compare adult stem cells to
embryonic stem cells. In the mouse it is very clear that in
embryonic stem cells, the capacity to grow, the persistence,
the reliability, the lack of genetic problems, the question of
genetic mistakes or genetic damage in cells, and the true
pluripotentiality, the ability of those cells to give rise to
many, many different types of cell specificities or lineages
are superior characteristics to adult stem cells.
Senator Specter. I would like to have your verification and
comment on other statements made by you that in cancer
treatment you destroy cells. It is a destructive process to try
to eliminate cancer, and then the stem cells are critically
important as they come into the human body to replace the cells
which have been destroyed. Would you amplify on that please?
Dr. Klausner. Yes. We have talked a lot about the promises
of stem cells for a variety of different diseases. Most of
these diseases are degenerative diseases where you need to
replace cells, and so it is regenerative medicine, this hoped-
for field, that people put most of their hopes on for direct
impact of stem cells.
And as I have said to you, cancer is sort of the opposite.
It is not a degenerative disease; it is the opposite, a disease
where cells proliferate. But in that process normal tissues are
damaged, injured, or even killed both from the disease and from
the current therapy. So, the indirect place where stem cell and
regenerative medicine is hoped for to be helpful, or useful, in
cancer would be to replace damaged tissue.
Senator Specter. One final question. The yellow light just
turned to red, but let me ask just one final question. And that
is, from your letter, you make the comment, probably the most
dramatic advancement is the drug Gleevec in the treatment of
CML. A two-part question. Absent the stem cells, could you have
had this dramatic advance and what are the prospects for stem
cells to be equally as effective on other forms of cancer?
Dr. Klausner. In the letter, I actually was referring to
hematopoietic stem cells, which can be adult stem cells.
Studying the derivation of the specialization of blood cells
from blood forming stem cells, which are adult stem cells and
not embryonic stem cells, allowed the research to go on to
understand the molecular changes that happen in CML, chronic
myelogenous leukemia. So, this was a general discussion of stem
cells. In that particular case, it was not embryonic stem cell
research, but rather adult stem cell research.
Senator Specter. Well, answer the second part. How badly
would you be disadvantaged if you could not use embryonic stem
cells in the work which you are pursuing with these very large
grants we have gotten for you?
Dr. Klausner. I think the reality is as a scientist, if we
cannot do experiments to compare embryonic stem cells to non-
embryonic or adult stem cells, we cannot answer the question
about what advantages they might have and what we may be
missing. As I said, our best experience is from the mouse where
the differences are quite clear and the advantages of embryonic
stem cells for scientific research are clear.
Senator Specter. Thank you very much.
Senator Harkin.
Senator Harkin [presiding]. Thank you very much, Senator.
Dr. Klausner, I just have one question. I wanted to get
into just one small area of this, but it is a very important
area, again a report that came out in the Washington Post
yesterday. It was the National Cancer Policy Board had a report
that said that we are focused so much on finding a cure that we
are neglecting research in how to care for people who are
dying. The report noted that NCI spent less than 1 percent of
its 1999 budget on research and training related to palliative
care.
This is an important topic for this hearing because so many
people are living with incurable blood cancers. Of course, we
do not want to cut down the research on finding the cure, but
what can we do to help the people who today are living it deal
with the pain and the depression and other symptoms?
I noted that in the press report yesterday, it quoted you
as saying that you were very enthusiastic about the report and
that you are planning to convene a group to determine how to
implement its recommendations. I just wonder if you have
anything else that you could tell us about how you plan to
proceed on this.
Dr. Klausner. This is a very important report, and it does
suggest that all of us need to pay more attention to this. The
National Cancer Policy Board, which raised this issue, was
actually an idea of mine and I went to the academy to have this
set up to provide to the Nation advice about policy issues
relevant to cancer that not only affect NCI but actually affect
all aspects of decision making in the Federal Government and
outside the Federal Government.
This issue of end of life and palliative care is a critical
one. We do need to do more research. I am really pleased with
the recommendations that the Policy Board has made. Many
members of the Policy Board are on our advisory committees. We
met last week and we will be looking at ways that we can act on
their recommendations to increase research in this area.
Senator Harkin. I appreciate it. If there is anything this
subcommittee can do to be helpful, please let us know.
Dr. Klausner. Thank you.
Senator Harkin. I would now recognize Senator Hutchison.
Senator Hutchison. Thank you, Mr. Chairman, and thank you
for holding this hearing, along with Senator Specter. It was a
great team effort.
Dr. Klausner, I wanted to ask you specifically what you see
going forward with the recommendations of the Progress Review
Group and if you foresee the NCI going in a certain direction
in advancing research on the blood cancers now and in the near-
to mid-term.
Dr. Klausner. One of the things that I felt about the PRG
group, which was a terrific group, and was very satisfying,
although you may want to hear from them, was the very nice
alignment between their recommendations of where we need to go
and the dozens of new programs that we have put in place at NCI
to capture the possibilities of new science, new ways of asking
questions, to direct them specifically to blood malignancies. I
think the PRG recognized that we had set up these structures
and we were really set to go, and with these explicit
recommendations, we already are working with the members of the
PRG within the NCI to figure out what needs to be initiated,
what needs to be expanded, and what we will be able to afford
to do.
What I really like about the PRG report is the clarity with
which it describes how we are going to capture the types of
scientific possibilities that I just briefly touched on at the
beginning of the hearing in order to make progress. So, we have
been mapping all of their recommendations, every single one,
against our initiatives, our mechanisms of funding, our funding
areas, and then we will be meeting with the PRG group again
soon, when we will agree on the mapping and the prioritization
of how to go forward.
Senator Hutchison. In the last 3 years, it seems that there
has been more success at stemming the fatalities, the mortality
of the blood cancers. I just wondered if that means that you
can do more in research because you have started to build a
solid base of research? And where do you think the most
promising avenues of research are in the near-term future?
Dr. Klausner. Well, I think there are two issues. One, I
think we finally have the tools to correctly classify and
diagnose these diseases. I know that sounds very abstract, but
if we do not have the right diagnosis for a disease, you cannot
actually figure out the right treatment. This is the
characteristic of modern medicine. For the first time we
believe we have definitive, new tools to correctly classify all
these different diseases. Is myeloma one disease? Is it two
diseases? Is it five diseases? And it is very hard to find a
single treatment for many different diseases.
So, that is the first thing that we have now available to
us and if we had enough time, which we do not, we could talk
about exactly what we have put in place to challenge the
community. In fact, it is a large program around the country
called the Director's Challenge where we put out money to
definitively molecularly classify all of these diseases for the
first time in history.
Then the second part is to finally make use of knowing the
difference between each disease. What precisely is wrong in
each disease? We need to know the molecular machinery, just
like we need to know the machinery that is wrong in a car if we
are going to fix it. And finally we need a set of drugs or the
immune system to not non-specifically try to kill the cancer,
which often does not work, but to very specifically go after
what is different between the cancer and the non-cancer, the
way antibiotics go after the difference between bacteria and
human cells. It is in that arena that we really expect to move
forward.
Senator Hutchison. Let me just end, because my time is just
about up, by asking you a simple question. Are you willing to
say that you will be able to put more focus on these blood
cancers now that you do have a little more to go on?
Dr. Klausner. Oh, absolutely.
Senator Hutchison. Thank you very much.
Senator Harkin. Thank you, Senator Hutchison.
Senator Murray.
Senator Murray. Thank you very much, Mr. Chairman, and
thank you for accommodating all the people now. I can see that
my constituents have made it into the back of the room and I am
delighted.
Senator Specter. Senator Murray, there is no one in the
hall. We have a lot of people sitting. We brought the last
group in to sit on the floor up front.
Senator Murray. I appreciate it. As some of you know,
traveling 3,000 miles to get to a hearing is a large
undertaking. These people have made a tremendous effort. So, I
appreciate your allowing them in.
I just have one question for Dr. Klausner. I know we have a
number of other panels.
I am delighted we have been joined by Senator Mikulski who
has been such a great, great advocate for these issues for a
long time. I will just ask one so she can get to hers.
I just wanted to ask about one of the contentious issues
that is contained in the McCain-Edwards-Kennedy Patients' Bill
of Rights that we have been discussing on the floor of the
Senate, and that is access to clinical trials and innovative
new treatments. Some of the opponents of the legislation have
been arguing that access to clinical trials is too costly. It
seems to me that if we save lives and move forward, that those
costs are offset.
But could you just talk for a minute about how important
clinical trials are in treating blood-related cancers?
Dr. Klausner. Yes, I feel very passionate about this. All
of the progress we have made, when we have made progress, is
the result of clinical trials. We will not make progress
without clinical trials. I think it is wrong and unfair to deny
patients access to clinical trials.
But we have also studied this issue whether care in the
context of a cancer clinical trial is more expensive than care
outside the clinical trial. We have done at least four studies.
We are waiting for a much larger study we have done with the
RAND Corporation, and every study shows that there are no
significant added clinical costs. So, I think the cost argument
is unacceptable, and I think we need to move to make sure that
patients are not denied that opportunity for themselves as well
as to contribute to society at large.
Senator Murray. Thank you very much. I appreciate that
response.
Thank you, Mr. Chairman.
Senator Harkin. Thank you very much, Senator Murray.
Senator Mikulski.
STATEMENT OF SENATOR BARBARA A. MIKULSKI
Senator Mikulski. Thank you very much, Mr. Chairman. First
of all, let me thank you for affording me the courtesy of
participating with this subcommittee. Though I am an
appropriator, I am not a member of this subcommittee.
I hope though, as the chair of the VA/HUD appropriations
subcommittee, that we could have lessons learned from this
hearing on how there could be applicability for the information
in veterans' health care, in terms of detection, treatment, and
certainly on VA clinical research.
I am here because I want to learn. I am a very proud
cosponsor of the Hutchison bill. I want to learn because, like
all of us, we come because it affects people in our family. A
very close member of my family is Geraldine Ferraro. I regard
her like a sister, and when I heard of this information and her
situation, I was determined to work on a bipartisan basis on
this.
I know that we are going to hear testimony from Mr. Larry
Lucchino, who used to be in Baltimore with the Orioles and now
is CEO with the Padres. We went out in Little Italy together.
We drank wine.
I even took him to an inaugural dance, and here we are. But
he has gone on to another life and love. And, well, I am an
appropriator.
So, I am just happy to be here. I am going to waive my
questions to Dr. Klausner. We meet often and talk, and I know
the subcommittee is running late.
But, again, thank you so much and I will have other
questions.
Senator Harkin. Thank you very much, Dr. Klausner, for
everything. We will dismiss you and we will bring up the next
panel: Dr. Sandra Horning, Mr. Larry Lucchino, Dr. Hagop
Kantarjian, Mr. Miles Pendleton, Jr.
Because of the tightness of time--11:30 we have a full
committee hearing that we must tend to--I am going to ask if
each person can just try to limit it to 4 minutes. I am going
to try to get this timer light, if I could. I hate to do that,
but it is just simply a time problem. We will move ahead as
aggressively as possible.
When you finish, if you could come up here and sit
someplace. Those of you in back, we have some empty seats up in
front. So, those who may really need to sit down, please come
up here and take some of the seats.
So, we will start with Dr. Sandra Horning, Professor of
Medicine, Stanford University, a member of the Board of
Directors of the American Society of Clinical Oncology, and as
I said, from my back yard of Creston, Iowa. Dr. Horning.
STATEMENT OF SANDRA J. HORNING, M.D., STANFORD
UNIVERSITY SCHOOL OF MEDICINE
Dr. Horning. Thank you. As stated, I am a professor of
medicine at Stanford University where I do clinical research in
Hodgkin's disease and non-Hodgkin's lymphoma. I am also pleased
to serve on the Scientific Advisory Board of the Cure for
Lymphoma Foundation and also as a member of the Board of
Directors of the American Society of Clinical Oncology.
Mr. Chairman, I would like to thank you and your
colleagues, Senator Specter and Senator Hutchison, for your
leadership in scheduling this timely hearing upon the release
of the Leukemia-Lymphoma-Myeloma Progress Review Group report.
As you have heard we are currently poised to make significant
advances in the treatment of blood-related cancers. I am
especially honored to appear before a fellow Iowan with a
strong commitment to biomedical research, and as this
represents my own 5-year survivorship of malignancy, I also
identify strongly with the large number of advocates present
here today.
Lymphoma, as you heard, with some introduction from Dr.
Klausner, is a general term for cancer of the lymphatic system,
which is part of the immune system. There are two-broad based
categories of lymphoma, the relatively common non-Hodgkin's
lymphoma, which I will refer to as lymphoma and the more rare
Hodgkin's disease.
From 1973 to 1998, the incidence rate for lymphoma
increased by 83 percent with the current estimate of more than
56,000 cases annually. This is actually the highest rate of
increase for any cancer, an increase that is unexplained.
Further, lymphoma represented the second greatest increase in
mortality among all cancers over the same period. The success
of treatment varies with an overall 5-year survival rate of 54
percent.
The lymphomas are complex disorders with more than 30
unique subtypes. As you have heard, molecular profiling of the
lymphomas is now underway on a large scale. This work promises
great benefits for diagnosis and new targets for therapy, but
it also poses a significant challenge, the challenge inherent
in conducting clinical research for rare diseases.
There is great enthusiasm for the new immunotherapies
modeled after the body's own immune system that are
revolutionizing the treatment of lymphoma. The monoclonal
antibody Rituxan targets the marker on the surface of 80
percent or more of the lymphomas. Because antibodies like
Rituxan have few side effects, they are favored by patients and
they can be combined with chemotherapy or radiation therapy.
Several new antibodies that target different markers
expressed on lymphoma cells are being tested currently in
clinical trials. Antibodies can also be used as a targeted
delivery system for toxins or radiation. Two new products,
Bexxar and Zevalin, combine a radioisotope with an antibody
targeted to B-cell lymphoma. Promising data from clinical
trials has been reported with both.
Recent technological advances have made it possible to
custom-make vaccines for B-cell lymphoma on a scale sufficient
for testing in large clinical trials. These vaccines are
designed to stimulate an anti-lymphoma effect among patients in
remission after chemotherapy, but destined to relapse after
conventional treatment.
Discoveries in lymphoma and other hematologic cancers have
often blazed the trail for the common solid tumors, and it is
our belief that the pioneering development of immunotherapy for
lymphoma will also lead to improved treatments in other
cancers.
I see my light is turning red.
I want to put a plug in for the integral role of clinical
research that has been mentioned. It represents a major success
of the federally supported cancer program. However, clinical
research in rare diseases can be a daunting task due to the
time and costs involved. The participation of community
oncologists is absolutely critical to timely and full accrual
to clinical studies in lymphoma and Hodgkin's disease. Thus,
appropriate allocation of resources to the design,
organization, and execution of clinical research in the
community is needed.
The NIH and the pharmaceutical industry are important
partners in drug development and clinical research. We believe
for that reason that the Patients' Bill of Rights must include
comprehensive coverage of cancer clinical trials, coverage that
would ensure access to both FDA-sponsored and Government-funded
trials.
On behalf of all of us who are passionate about
understanding and effectively treating the hematologic cancers,
researchers, the 700,000 patients who currently have these
diseases, and their practitioners, I would like to thank you
for holding this hearing. The hematologic cancers pose serious
challenges and offer unprecedented opportunities.
May I just have 30 more seconds?
Senator Harkin. Yes.
Dr. Horning. Thank you.
PREPARED STATEMENT
So, our recommendations are to implement the
recommendations of the Progress Review Group, to heighten
efforts to identify the reasons for the increased incidence of
lymphoma, to improve coordination among the NCI, FDA, and the
pharmaceutical industry, and enactment of the Patients' Bill of
Rights with comprehensive clinical trials coverage.
Thank you.
[The statement follows:]
PREPARED STATEMENT OF SANDRA J. HORNING
Good morning, I am Dr. Sandra J. Horning, Professor of Medicine at
Stanford University School of Medicine. My clinical research in
Hodgkin's disease and non-Hodgkin's lymphoma (NHL) focuses on improving
therapeutic outcomes, reducing treatment complications, and elucidating
the biology of the diseases. I am also pleased to be here today in my
capacity as member of the Scientific Advisory Board of the Cure For
Lymphoma Foundation, an organization that supports lymphoma research
and education, and as a member of the Board of Directors of the
American Society of Clinical Oncology (ASCO), the world's leading
medical specialty society for cancer researchers.
Mr. Chairman, I would like to thank you and your colleagues,
Senator Specter and Senator Hutchison, for your leadership in
scheduling this hearing on hematological cancer research. This hearing
is timely because the report of the Leukemia-Lymphoma-Myeloma Progress
Review Group (LLM-PRG) has just been published and because we are
poised to make significant advances in the treatment of blood-related
cancers. We welcome the opportunity to review recent research progress
and consider policy changes that might accelerate the development of
new treatments for these cancers.
As a native of Creston, Iowa and graduate of the University of Iowa
School of Medicine, I am especially honored to appear before a fellow
Iowan. Your strong commitment to biomedical research has ensured that
we have the financial resources to support basic biomedical research
and to expand the clinical trials network of the National Cancer
Institute (NCI) across the nation. A balanced approach of support for
basic and clinical research is essential to achieving improvements in
the treatment of all cancers.
A LYMPHOMA PRIMER
Lymphoma is a general term for cancer of the lymphatic system,
which is part of the immune system. There are two broad categories of
lymphoma, one relatively common--non-Hodgkin's lymphoma, or NHL, and
one relatively rare--Hodgkin's disease. There are approximately 64,000
cases of NHL and 7,400 cases of Hodgkin's disease diagnosed annually in
the United States. Taken together, lymphomas rank as the fifth most
common cancer behind prostate, breast, lung, and colorectal cancer.
The non-Hodgkin's lymphomas (NHL) are categorized based on their
appearance under the microscope and their expression of immune system
markers, which allows them to be classified as originating from B- or
T-cells. These are complex disorders, with more than 30 unique
subtypes. Some NHL grow and spread quickly, whereas others develop more
slowly. Thus, the NHL have been broadly characterized as aggressive or
indolent. Utilizing current technology to assess the expression of many
genes, potential new subtypes of NHL have been identified based on
molecular ``profiles.''
Between 1973 and 1998, the incidence rate for NHL increased by 83
percent, the highest rate of increase for any cancer. Although
occupational exposure to chemicals has been implicated, the increased
incidence of NHL is unexplained. The importance of NHL is highlighted
by the fact that this disease also represented the second greatest
increase in cancer mortality over the same period. The treatments for
NHL include radiation, chemotherapy; stem cell transplantation; and
immunotherapy. The success of treatment varies according to NHL subtype
and clinical features, resulting in a collective five-year survival
rate of only 53 percent.
In contrast, the incidence of Hodgkin's disease has been stable and
the five-year survival rate has improved steadily to the current figure
of 85 percent. However, Hodgkin's disease remains a very important
disorder because the young patients with this disease, median age less
than 30 years, may have serious long-term adverse effects, such as
second cancers, as a result of chemotherapy and radiation treatments.
Studies of risk assessment, risk reduction and prevention are critical
not only to the long-term survivors of Hodgkin's disease but for all
cancer patients treated with chemotherapy and radiation therapy.
LYMPHOMA SUBTYPES
Significant insights into the underlying biology of the NHL have
resulted from recent research efforts. In work that Dr. Richard
Klausner has already described, researchers at the NCI, Stanford, and
the University of Nebraska and other institutions utilized microarray
technology to assess gene expression in the most common NHL subtype,
diffuse large B-cell lymphoma.
This research suggested that the clinical behavior of diffuse large
B-cell lymphoma corresponds to the expression of genes in the immune
cell of origin, such that two distinct diseases were identified. For
patients with one subtype, roughly three-quarters were alive five years
after chemotherapy, whereas less than one-quarter of those with the
other subtype were alive five years after treatment.
Currently, molecular profiling of lymphomas and leukemias is
underway on a much larger scale. This work promises not only to help
determine prognosis for individual patients but to provide new
therapeutics targeted to the underlying biology. Ultimately, research
initiatives will be more focused, physicians will assist patients in
making more informed decisions, and the survival of NHL patients will
improve.
Although molecular sub-typing of NHL will surely yield important
benefits, it also poses significant research challenges. The further
sub-classification of NHL changes a collectively common cancer into
many orphan diseases, with all the challenges inherent in conducting
clinical research for rare disorders. The same circumstance will
ultimately be true of the most common cancers as their biology is
further understood. Thus, it is important to address this challenge
with the NHL here and now.
CURRENT TREATMENT OPTIONS AND TREATMENT ADVANCES
Treatments for NHL have traditionally included chemotherapy and
radiation therapy. For those with recurrent lymphoma, high dose
chemotherapy or radiation with stem cell transplantation may be a
treatment option.
New immunotherapies, modeled after the body's own immune system,
are revolutionizing the treatment of NHL. A monoclonal antibody called
Rituxan is approved for the treatment of recurrent, indolent B-cell
non-Hodgkin's lymphoma. Rituxan targets a B-cell antigen, CD20, found
on normal and malignant B-cells. (Because the youngest B cells do not
express the CD20 antigen, normal B-cells regenerate after treatment).
In addition to killing lymphoma cells by traditional immune mechanisms,
Rituxan may send a direct death signal. Most exciting, antibodies like
Rituxan have few side effects, allowing their combination with
chemotherapy or radiation therapy. Some studies already demonstrate a
benefit for such combinations compared with conventional therapies.
Several new monoclonal antibodies that target different antigens
expressed on B- and T-cells are being tested in clinical trials. These
new therapeutics create the possibility of ``combination
immunotherapy.'' Antibodies can also be used as a targeted delivery
system for cell toxins or radiation. Bexxar and Zevalin are two
products in advanced stage of development that combine a radioisotope
with a monoclonal antibody targeted to the CD20 antigen of B-cells.
Promising data from clinical trials has been reported with both of
these new agents.
Vaccines derived from the B-cell antigen that is unique to an
individual's NHL have been applied after conventional chemotherapy for
indolent lymphoma. Recent technological advances have made it possible
to ``custom make'' these vaccines on a scale sufficient for testing in
large clinical trials. Based on preliminary studies, researchers hope
these vaccines will have an anti-lymphoma effect for patients with
minimal disease or in remission but destined to relapse after
conventional treatment.
It is our hope that these immunotherapies, used as a complement to
other therapies or in combination with other therapies, will
significantly and favorably impact the survival rates for NHL. In
addition to their therapeutic promise, immunotherapies have fewer and
less severe side effects than those of chemotherapy and radiation.
The moderation or elimination of the serious side effects of
treatment is of great concern to patients. As mentioned, success in
treating Hodgkin's disease has been accompanied by serious adverse
effects, including second cancers, sterility, organ dysfunction, and
psychosocial effects, all of which impact quality of life. It is
imperative that we strive not only for cures, but also for the least
complicated cures, in our research efforts.
Discoveries in lymphoma and other hematological cancers have often
blazed the trial for the common solid tumors, and it is our belief that
the pioneering development of immunotherapy for lymphoma will also lead
to improved treatments in other cancers.
CHALLENGES FOR CLINICAL RESEARCH IN LYMPHOMA
The integral role of clinical research in patient care represents a
major success of the federally supported cancer program. In a 1998 ASCO
(American Society of Clinical Oncology) survey, more than 80 percent of
physicians indicated that they enroll patients in clinical trials. The
active participation of the academic and community oncologist in
clinical research is essential for the rapid clinical testing of
promising new therapies. Patients often make decisions about enrollment
in clinical trials, which may represent the best treatment option, in
consultation with a community oncologist.
Despite the enthusiasm among oncologists regarding clinical
research, there are obstacles to participation that result in a small
percentage of eligible patients who actually enroll in clinical trials.
The ASCO study of clinical trials uncovered serious strains in this
system, including the fact that oncologists often receive inadequate
reimbursement for the costs of enrolling patients in clinical trials.
In addition to the added time to inform and consent patients, fixed
costs associated with enrolling patients in trials include the approval
of trials by an institutional review board (IRB), data management
requirements during and after treatment, and the reporting of adverse
events.
These obstacles become more daunting in rare disorders, where the
time and costs may prove overwhelming for busy practitioners. As we
move toward the subclassification and further sub-classification of
cancer, first with the NHL and later with other cancers, these issues
must be addressed in order to promote clinical trials of new therapies.
The participation of community oncologists is absolutely critical to
timely and full accrual to clinical studies in NHL and Hodgkin's
disease. Thus, appropriate allocation of resources to the design,
organization and execution of clinical research in the community is
needed.
ROLE OF INDUSTRY IN CLINICAL RESEARCH
Support of basic biomedical research and a nationwide clinical
trials network by the National Institutes of Health (NIH) and support
of clinical research by the pharmaceutical industry represents an
important partnership. The pivotal trials of new agents are often
conducted exclusively by industry, with Rituxan and Gleevec as recent
examples. Subsequently, important trials for new indications of
approved drugs frequently emanate from the cooperative groups, as
evidenced by multiple ongoing trials incorporating Rituxan in NHL.
The translation of basic research into new NHL treatments occurs in
academic research centers like Stanford (usually the result of NIH
funding), small biotechnology companies, and large pharmaceutical
companies. The new immunotherapies--Rituxan, Bexxar, Zevalin, as well
as new lymphoma vaccines--represent the results of this partnership.
Both patients and physicians prize access to industry-sponsored
trials. For patients, they often represent the only avenue to
potentially life-extending new agents. Physicians wish to offer their
patients novel therapies at the earliest possible time. Industry trials
are attractive because they are designed and conducted with a sense of
urgency, leading to timely results. Significantly, industry trials pay
for enrollment of patients at a rate that approximates the actual cost
of necessary clinical trial activities. In contrast, the ASCO study
found that reimbursement rates for these activities in NCI-sponsored
trials were well below the actual costs incurred by physicians.
Thus, industry-sponsored trials play an essential part in the
overall clinical research enterprise and should not be considered of
lesser significance than trials sponsored by NIH. It is for this reason
that the cancer community has advocated a clinical trials coverage
provision in the various Patients' Bills of Rights that would ensure
access to industry-sponsored as well as government-funded trials. When
Congress eventually passes a Patients' Bill of Rights, it must include
comprehensive coverage of cancer clinical trials.
RESEARCH RECOMMENDATIONS OF THE LLM-PRG
Researchers and advocates commend the NCI for convening the
Leukemia, Lymphoma, and Myeloma Progress Review Group (LLM-PRG),
comprising more than 180 researchers, clinicians, patient advocates,
industry representatives, and government officials. In May 2001, this
group released its evaluation of research on hematologic malignancies.
One of the most important benefits of the PRG process is its
inclusion of advocates in the deliberations. Advocates brought to the
PRG deliberations a sense of urgency and an insistence on removal of
bureaucratic barriers to the development of new therapies.
The core recommendations of the PRG relate to methods for
shortening the time for translating basic research findings into new
treatments. Among the research and development strategies identified in
the PRG report are:
--Fostering partnerships among NCI, academics, advocates, cooperative
groups, the Food and Drug Administration (FDA) and industry;
--Developing education and training programs for certification of
physicians and centers for diagnosis, treatment, and clinical
trials in hematological malignancies
--Establishing innovative new research mechanisms to foster
collaboration among experts from multiple disciplines and
institutions.
New treatments, in many cases, may be integrated with established
treatments. Appropriate allocation of resources to the design,
organization and execution of clinical research in the community is
needed to study the resultant, multiple combinations and permutations.
The advocates emphatically endorse improved communication between
physician and patient regarding increasingly complex treatment
decisions. Further, the advocates strongly support research efforts
directed toward the late effects of treatment.
RECOMMENDATIONS FOR CONGRESSIONAL ACTION
On behalf of all of us who are passionate about understanding and
effectively treating the hematologic cancers--patients, researchers,
and practitioners--I would like to thank you for holding this special
hearing to consider the state of their research.
The hematological cancers pose serious challenges and offer
unprecedented opportunities. The incidence of NHL is increasing for
reasons that we do not understand and the five-year survival rates for
NHL, myeloma, and leukemias remain unacceptably low. Breakthroughs in
molecular diagnostics promise new, targeted treatments based on
increased understanding of the biology of these diseases. Meanwhile the
era of specific immunotherapy has begun with resounding success and we
see much more on the horizon. In order to accelerate the realization of
these unparalleled opportunities, we recommend several actions by
Congress to improve the environment for research on lymphoma and the
other blood-related cancers:
--Implementation, facilitated by the NCI, of the collaborative
strategies for research and development of hematological cancer
therapies recommended by the LLM-PRG;
--Heightened efforts to identify the reasons for the increased
incidence of lymphoma; Improved coordination among NCI, FDA,
and industry to bring new drugs to market sooner;
--A system of payment for enrolling patients in lymphoma clinical
trials commensurate with their complexity and costs; and
--Enactment of a patients' bill of rights with comprehensive clinical
trials coverage, including industry-sponsored trials under
regulatory authority.
This is an exciting time to be involved in research on
hematological cancers. I would again like to express the deep
appreciation of the research community for the strong Congressional
support for biomedical research. We look forward to a continued strong
partnership, advancing our understanding of cancer, developing new
therapies, and rapidly testing these new treatments in patients,
continually striving for cures with the best quality of life.
Senator Harkin. Thank you very much, Dr. Horning. I had to
cut you off. They would think I was playing favorites if I let
you go on.
Mr. Lucchino.
STATEMENT OF LARRY LUCCHINO, PRESIDENT AND CEO, SAN
DIEGO PADRES
Mr. Lucchino. Yes, good morning. I am Larry Lucchino. I am
the president and CEO of the San Diego Padres. I speak to you
today as a survivor of non-Hodgkin's lymphoma in the 1980's and
prostate cancer in the 1990's. I would like to thank you as
well for the opportunity to discuss my experiences and to
highlight the need for strong Federal support for biomedical
research.
Senator Harkin, I would like first to thank you and to
thank Senator Specter, Senator Hutchison, Senator Murray, and
my old, dear friend, Senator Mikulski, for your strong interest
in leukemia, lymphoma, and myeloma. These diseases have been
too long off the radar screen. As a Pittsburgh native, I would
especially like to salute Senator Specter from my home State
for his leadership in the fight for biomedical research.
In the fall of 1985, I was diagnosed with non-Hodgkin's
lymphoma. I was told the odds were very much against me. I went
to a physician to determine the source of a persistent cough
and was given a life-altering diagnosis. I was told only one-
third of us would survive. Fortunately, I was referred to the
great Tom Fry and the Dana-Farber Cancer Institute in Boston
where I underwent aggressive chemotherapy and an autologous
bone marrow transplant. As I recall, I was only the 33rd
patient to receive this treatment at Dana-Farber. Bone marrow
transplantation, an experimental for lymphoma 15 years ago, is
now considered standard treatment around the country for
thousands of lymphoma patients.
Almost a decade and a half after that experience, the
numbers on non-Hodgkin's lymphoma do not tell a promising
story. As Dr. Horning referred to, between 1973 and 1998, the
incidence rate for non-Hodgkin's lymphoma increased almost 83
percent. The 5-year survival rate for non-Hodgkin's lymphoma
still hovers at about 54 percent. For those who are treated
successfully, the long-term side effects can be devastating.
I applaud the NCI for convening its blue ribbon panel to
review the current program on lymphoma, leukemia, and myeloma
and proposing new strategies for accelerating the translation
of basic research findings into new treatments. My own
physician, the inestimable Dr. Lee Nadler of Dana-Farber, was a
member of that group, so I know it took an aggressive approach.
My message today is simple. We must accelerate the research
and development process, and we need to do it now. For those of
us who have been diagnosed with cancer, time is a precious
commodity. We believe that old structures must be reformed and
new systems created to bring treatments to patients at a faster
pace. The time and distance from a scientist's laboratory bench
to the patient's bedside must be shortened.
The NCI's blue ribbon panel specifically emphasized
collaboration and cooperation among researchers, industry,
Government, and advocates. I would like to specifically
acknowledge the contribution of the Cure for Lymphoma
Foundation, a private organization that funds research, as an
example of the partnership that will be critical to moving the
research agenda forward.
More specifically I would like to recommend some concrete
action steps.
Please maintain a strong Federal role in the funding of
biomedical research.
Please implement a balanced approach of support for basic
and clinical research so that laboratory discoveries can be
translated quickly.
Please develop a budget for the recommendations included in
the PRG panel and hold the NCI accountable for implementing
that research plan.
Please encourage additional collaboration between the
private and the public sectors, between industry, academia, and
the Government. We need a new alliance.
Please implement on a pilot basis new methods for
evaluating and collaborating in research.
Senator Specter [presiding]. Mr. Lucchino, I am very
reluctant to interrupt anyone, especially an ex-Pennsylvanian.
But we are on a very tight time table and have to be at a
markup on the supplemental. So, we are going to have to ask you
to take 30 more seconds.
Mr. Lucchino. I will do so. Thank you.
Senator Specter. We are going to have to ask everybody else
to observe the red light meticulously. Thank you.
PREPARED STATEMENT
Mr. Lucchino. I would like to make perhaps a reference to
the sports world in which I operate these days. It is a real
privilege and I think a duty for someone in the toy department
of life, the world of baseball, to come and have a chance to
contribute to issues as important to all of this. Perhaps I can
take from the sports world an expression, if Nike will excuse
the borrowing. Life is short; research hard.
Thank you very much for this opportunity.
[The statement follows:]
Prepared Statement of Larry Lucchino
Good morning, I am Larry Lucchino, President and CEO of the San
Diego Padres. I speak to you today as a survivor of non-Hodgkin's
lymphoma in the 80's and prostate cancer in the 90's. I would like to
thank you for this opportunity to discuss my experiences and to
highlight the need for strong federal support for biomedical research
and innovative strategies for public and private research partnerships.
Senator Harkin, I would like to express my appreciation to you,
Senator Specter, and Senator Hutchison for your strong interest in
cancer research and your willingness to hold this special hearing
focusing on leukemia, lymphoma, and myeloma. As a Pittsburgh native, I
would especially like to salute the senior Senator from my home state
of Pennsylvania, Senator Specter, for his leadership in the fight for
federal funding for biomedical research.
TREATMENT FOR NON-HODGKIN'S LYMPHOMA
When I was diagnosed with non-Hodgkin's lymphoma in the fall of
1985, I was told that the odds were very much against me. I went to a
physician to determine the source of a persistent cough and was given a
life-altering diagnosis. Fortunately, I was referred to the great Dana-
Farber Cancer Institute in Boston, where I underwent aggressive
chemotherapy and an autologous bone marrow transplant. As I recall, I
was only the 33 patient to receive this treatment at Dana-Farber. Bone
marrow transplantation, an experimental treatment for lymphoma 15 years
ago, is now considered standard treatment for certain lymphoma
patients.
Just two years ago, I was diagnosed with prostate cancer and
underwent treatment at Johns Hopkins. I will focus my remarks today on
lymphoma and the other blood-related cancers, but the research
strategies and public policies that will make a difference for lymphoma
patients will also make a difference for prostate cancer patients and
all other cancer patients, as I understand that discoveries in lymphoma
have frequently pioneered advances in other cancers.
The numbers on NHL do not tell a promising story. Between 1973 and
1998, the incidence rate for non-Hodgkin's lymphoma increased almost 83
percent, among the highest rate of increase for any cancer. For that
same time period, the death rate for NHL increased by 45 percent.
Although significant progress has been made in treatments for some
cancer, including Hodgkin's disease and certain childhood leukemias,
the five-year survival rate for non-Hodgkin's lymphoma still hovers at
about 54 percent. Even for those who are treated successfully, the
long-term side-effects can be devastating.
The challenges are obvious. We must still answer fundamental
questions about the causes of NHL and at the same time accelerate the
pace of development for new treatments.
ADVANCES IN LYMPHOMA RESEARCH
In the last several years, there have been some important
developments in the treatment of NHL. The most promising broad category
of treatments are those that are referred to as immunotherapies, or
therapies that utilize the body's own immune system to fight cancer. A
monoclonal antibody has been approved for the treatment of a form of B-
cell lymphoma, and radioimmunotherapies, which combine monoclonal
antibodies with radiation, are in development for the same type of
lymphoma. Monoclonal antibodies for additional forms of lymphoma are
being investigated, and researchers are designing and testing vaccines,
which are created for each individual from the tissue from his or her
tumor.
There is great hope that these treatments will improve the outlook
for lymphoma patients, but it is still too soon to know if they will
have a significant impact on the lymphoma survival rate.
CONVENING OF A BLUE RIBBON PANEL
The National Cancer Institute (NCI) deserves commendation for
convening a blue ribbon panel to review its current program of research
on lymphoma, leukemia, and myeloma and to propose new strategies for
accelerating the translation of basic research findings into new
treatments. I was not a participant in this group, but I was pleased to
learn that cancer survivors like myself were an integral part of the
deliberations and that my own physician, the inestimable Dr. Lee Nadler
of Dana-Farber Cancer Institute, was a member of the group.
I have read the recommendations of the blue ribbon panel, and I
believe they point us in an important direction for hematological
cancer research. However, I would like to echo a theme that was central
to the report, a theme that I imagine was pressed by the cancer
survivors and other advocates: accelerate the research and development
process. And please do it now!
For those of us who have been diagnosed with cancer, time is a
precious commodity. We believe old structures must be reformed and new
systems created to bring treatments to patients at a faster pace. The
report emphasizes collaboration and cooperation among researchers,
industry, government, and advocates to achieve this goal.
I would like to acknowledge the contribution of the Cure For
Lymphoma Foundation (CFL), a private organization that funds research
and supports educational and informational programs for physicians,
researchers, patients, and their families. CFL and other private
organizations like it make a valuable contribution to the field, and
their financial resources are an important complement to federal
research funding. This is but one example of the partnership that will
be critical to moving the research agenda forward.
ACTION ON THE RECOMMENDATIONS
I would like recommend some concrete action steps if I may:
1. Maintain a strong federal role in the funding of biomedical
research. The Congress and Bush Administration have committed to
doubling the budget between 1999 and 2003, but there appears to be no
plan beyond that time. To prevent disruption in research and sustain
the progress we are making, Congress and the Administration must
develop and endorse a funding strategy beyond 2003.
2. Implement a balanced approach of support for basic and clinical
research so that laboratory discoveries can be translated into improved
patient outcomes.
3. Develop a budget for the recommendations included in the Blue
Ribbon Panel, and hold the NCI accountable for implementing the
research plan offered by the leaders in lymphoma, leukemia, and myeloma
research.
4. Encourage additional collaboration between the private and
public sectors. At present, new drug development is, at least
initially, almost exclusively the domain of pharmaceutical and
biotechnology companies. Basic science discoveries made in publicly
funded laboratories in academia and the National Institutes of Health
(NIH) could be translated by industry into clinical applications more
quickly if the flow of information were more efficient. This should be
a priority of NIH in order to ensure that the public benefits from the
nation's research investment at the earliest possible juncture.
5. Implement on a pilot basis, with rigorous methods for
evaluation, new structures for collaborative research. The patient
advocates in the PRG were captivated by the concept of a multi-
institutional and multi-disciplinary consortium that would accelerate
the drug development process. The Chronic Lymphocytic Leukemia Research
Consortium, centered at one of my favorite institutions, the University
of California at San Diego, may serve as a model for the kind of
collaboration involving researchers from different fields and different
institutions.
I was a healthy young man when I was diagnosed with non-Hodgkin's
lymphoma. Since my initial diagnosis, many more in the world of sports
have been diagnosed and treated for cancer, hockey players Mario
Lemieux and John Cullen, golfer Arnold Palmer and cyclist Lance
Armstrong. The first reaction for many of us was a desire to understand
why we had cancer, but for some of us that initial instinct has
developed into activism aimed not only at answering why we were
diagnosed with cancer but also aimed at educating the public about
cancer, solidifying support for federal funding of biomedical research,
and improving the environment for private sector research efforts. It
is my honor to be here with you today and to join with other advocates
in support of bold and creative approaches to cancer research. To
paraphrase an expression from the world of sports advertising, `` Life
is short; research hard (and fast).'' Thank you.
Senator Specter. Thank you very much, Mr. Lucchino.
Senator Harkin has had to leave us for other commitments,
and he has left the gavel in my hands.
STATEMENT OF MILES S. PENDLETON, JR.
Senator Specter. We turn now to Mr. Miles Pendleton, a
retired Foreign Service Officer, diagnosed with CLL leukemia in
1989 while serving in London. Mr. Pendleton is a graduate of
Yale, Harvard, and the National War College. Thank you for
joining us, Mr. Pendleton, and we look forward to your
testimony.
Mr. Pendleton. Thank you very much, Senator Specter. I
appreciate it.
I will not describe the disease. Think of CML without a
cure. Think of lots of us having pretty ugly chemo and
experiences that you can all imagine that go with it. From
looking at me, you can tell that I am perhaps a lucky person.
This room is full of courageous blood disorder patients who are
worse off than I am. Despite being heavily treated over the
years, I am determined to beat back this dragon with the help
of all of those who are doing CLL research. In the process, no
institution is more central than NCI and no army in the field
is more important than the recently established CLL Research
Consortium, which needs a higher level of funding now.
When I was first told that I had leukemia, I was running
the political section in London and I was called out of a
meeting, and a doctor told me on the phone, Mr. Pendleton, you
have leukemia, but it is chronic. It is the good kind.
Members of the committee, I can assure you there is no good
leukemia. I can also assure you that having leukemia is not
career-enhancing.
We are all encouraged to take a tape recorder to the first
meeting with the doctor who diagnoses us and invites us to come
in for a little chat about our blood tests. That is because
after we hear the word ``leukemia,'' we are not going to
remember a thing. I can guarantee you. Try it sometime.
A few words about CLL and the effort to cure it,
particularly through the Research Consortium funded by NCI. CLL
is the most common form of adult leukemia. More voters in your
States have it than any other form of leukemia. There are about
100,000 of us alive today. Nobody knows what triggers it, and
so there is not yet a Gleevec, but we are on the march. Nobody
knows what to target. Unfortunately, because of the toxins, we
are not living any longer than when I graduated from college 10
years ago--40 years ago.
I was just back at my reunion and it seems like 10.
It really destroys your life in many ways, a lot like AIDS.
But there is an accelerated measure of hope on the research
front through the consortium which brings together in an
unprecedented way institutions from Boston to La Jolla. It is
funded with a $16.5 million grant which sounds like a lot, but
it is split amongst nine institutions and to be spent over 4
years. Basically that ain't much. It is about what was spent by
Mrs. Casey to buy the site for the new mayor's residence here
in Washington.
To my astonishment, the consortium is unique in that for
the first time in NCI history it brings together the top
researchers from places like the Dana, from places like M.D.
Anderson. They are really making headway.
Senator Specter. Mr. Pendleton, the red light has been on.
Would you summarize please?
Mr. Pendleton. Yes. I will quote you.
Senator Specter. Take all the time you need.
Mr. Pendleton. You once said that druthers do not dollars
make. The consortium needs more dollars. It needs about $20
million now.
Thank you, Senator.
Senator Specter. Thank you, Mr. Pendleton.
We had a sense of a Senate resolution which expressed
druthers, but they do not translate to dollars. So, I think
that is where it ought to be identified.
PREPARED STATEMENT
Mr. Pendleton. Well, there is some report language out
there too which are druthers.
[The statement follows:]
Prepared Statement of Miles S. Pendleton, Jr.
Thank you Senator Harkin, Senator Specter, and members of this
Committee for inviting me to appear today. Right at the outset, I want
to say how much millions of patients and our families appreciate what
this Committee has done over the years for patients, medicine and
medical research.
My name is Miles Pendleton. For three decades I was a U.S. Foreign
Service Officer serving in the Department of State and in embassies
abroad. I visited with members of the Senate and House on many
occasions, both formal and informal. But, frankly, I am not entirely
happy to be appearing before you today because I do so as a leukemia
patient--no matter how robust I may appear at the moment.
I have long had and been treated for Chronic Lymphocytic Leukemia,
known as CLL. This is not CML, the chronic leukemia that may be cured
by the recently approved and much heralded pill called Gleevec. In CML
the target is known. In CLL it is not. I will focus on CLL.
In CLL patients, our bodies produce abnormal lymphocytes, a subtype
of white blood cells that migrate to the lymph nodes or other lymphoid
organs. They clog the body, crowding out the good cells in the blood
and marrow. They are relentless and refuse to die.
This is happening to my body, which is also residually impregnated
with a decade of toxins from oral chemo and infusions through the arm
that kill good and bad cells alike. As we say in the Foreign Service,
this is not ``career enhancing''.
Mr. Chairman, as you know, this room is full of blood disorder
patients, many who have come to Washington under the new umbrella of
Leukemia, Lymphoma, Myeloma-ACT to lobby for more research funding for
blood disorders. Many in this room are worse off than I am. I was
diagnosed years ago, in 1989, and despite many ups and downs, am still
kicking with a measure of ferocity. I can commiserate totally with
fellow patients who have engaged in bigger, more immediate, and more
desperate battles. In particular, I am in pain to find that that
distinguished American, Geraldine Ferraro, has reason to testify as a
patient today. She is an inspiration.
To many with CLL and other blood disorders, a twelve-year survival
must seem like a dream come true. It is. But I have had my turn at
harsh treatments with the resulting nausea, fatigue and mental
disorientation. Last time, it got bad enough that I could not ride on
the Washington Metro because the smell of the seats reminded me
powerfully of the chemo infusion chair. I will have my turn at heavy
treatment soon again--my turn to fight directly with what that
remarkable patient and CLL activist Barbara Lackritz calls ``our
dragon''.
I am determined to beat it back over and over again with the help
of all those who are doing CLL research, not only in the United States
but in the world. In that process, no institution is more central than
the National Cancer Institute, and no army in the field is more
important that the groundbreaking CLL Research Consortium, which needs
a higher level of funding now.
Let me tell you how I was told I have leukemia. At that time, I was
running the Political Section at the U.S. Embassy in London and
complaining of fatigue that led to a blood test. I was called out of a
meeting on the Human Rights Report to take a call from a doctor who
said--on the phone and all too briefly--that I had leukemia. But the
``good'' chronic kind. I should see a specialist. Soon I was told I
could expect to live five years or more. I heard five years. One of my
colleagues later told me that I seemed a bit disoriented when I
returned to the meeting. I did not tell him or anyone else but my wife
about the diagnosis.
I was 48. My wife and I suddenly had to ponder all those questions
about the future of our family and careers as we faced my mortality.
You can imagine what issues arise. If you can't, ask any one of many
patients in this room. We are all encouraged to take a tape recorder to
the first meeting with the doctor who diagnoses us and invites us to
come in for a little chat about out blood test--if we are not told on
the phone. That is because after we hear the word ``leukemia,'' we
generally will not remember a thing.
Mr. Chairman, you will recall that I was told I have a good
leukemia. There is no good leukemia or any other blood disorder. There
is no good cancer. As a doctor said at a conference at the National
Cancer Institute last week, the only good cancer cell is a dead cancer
cell. Another doctor told me that I am a lucky patient. And of course I
am. The fact that I am very much alive and generally thriving at age 62
means that I have not faced the ultimate immediacy of death that
Representative Joe Moakley bore with such grace and dignity.
Allow me to say a few more words about CLL and the effort to cure
it, particularly through the CLL Research Consortium funded by NCI--and
all the intramural and extramural research and researchers who are
working throughout the country and around the globe. As you listen to
these words about one subset of leukemia, CLL, please multiply by many
fold the impact on patients, families and the economy of blood
disorders and other forms of cancer.
CLL is the most common form of adult leukemia in the United States
and in the western world. More voters in each of your states have this
form of leukemia than any other. In the United States somewhat under
10,000 people are diagnosed with CLL each year, and 5,000 die. There
are about 100,000 of us alive at any given time. More men than women,
but women are hardly excluded. Unlike CML, nobody knows what triggers
CLL. Nobody really knows what to target, but CLL researchers are
getting closer every day. There are increasing indications that
environmental factors play a role in the process, causing abnormalities
in genes.
To date, CLL can not be cured. Indeed, those of us with CLL are not
living any longer in the aggregate than when I graduated from college
40 years ago. And this is despite intensifying and gratifying research
efforts and new but risky ways of managing the disease. For instance,
we have all heard about bone marrow transplants, but unfortunately
almost one quarter of those going the transplant route using marrow
from matching siblings are dying, usually from graft-versus-host
disease following the procedure.
Clearly CLL needs a Gleevec. We need a Gleevec in less than the 40
years it took to develop that drug. Breakthroughs may be near. We need
to know first what to target. And fortunately some extraordinary
genetic work is being done under the leadership of NCI and the CLL
Research Consortium in an effort to identify subgroups, targets and
cures like Gleevec. (Incidentally, Medicare will not cover Gleevec as a
pill. Only as an infusion via a vein. Legislation is needed to change
that, and it is needed now.)
CLL is not unlike AIDS in the way it destroys patients' health and
lives. It is quite parallel to the notion of starting with HIV and then
becoming full blown. The median age of diagnosis is 64. This may help
to account for the relative historic lack of public health concern
about the disease. However, a growing number of patients are being
diagnosed in their 30's and 40's. You will recall that I was diagnosed
at age 48.
CLL patients eventually have come to learn that while many of us
live only three to five years, many others survive for ten years--or
measurably longer. It depends on your subset and whether your CLL
mutates or not, markers that are only now becoming apparent.
And over time we come to cope with complications such as a
suppressed immune system, swollen lymph nodes, weakness, weight loss
(myself excluded so far). The most frequent immediate causes of death
are bleeding and systemic infections like pneumonia. CLL is truly a
devastating disease. Former Secretary of State Larry Eagleburger once
said to me ``You like wars'' as he moved me at the State Department
from the Falklands Island War Task Force to run the Office of Israel
and Arab-Israel Affairs when Israel was in Lebanon. However, this
cancer is a war that I would not have wished on anyone.
Mr. Chairman, I am glad to say that there is now a measure of hope
on the research front for CLL patients and their families. The
Committee's dedication to funding at adequate levels both NIH and NCI
has played a central role in this renewed hope. Everything you do to
increase funding for medical research translates directly or indirectly
into giving hope to patients in every state and around the world. I say
this as someone treated in Europe as well as the U.S.
There is report language going ahead in both the Senate and House
strongly encouraging NCI to give full and fair consideration to
expanding the scope of research activities through the CLL Research
Consortium that I have previously mentioned. But as Senator Specter has
said over the years about report language and sense of the Senate
resolutions, ``druthers do not make dollars''. If I had my druthers, I
would have Congress earmark $20 million more for the CLL Research
Consortium now, but I more or less understand the process. In this case
both Congress and NCI with its bypass budget and ability to make
decisions internally have to play a role.
This Consortium is a remarkable and long-overdue initiative. It is
worthy of more support now, and with the help of doctors, I calculate
that it could very usefully expend the $20 million I mentioned
previously And use it fruitfully now. NIH and NCI have, of course, long
sponsored really productive intramural and extramural research on CLL.
But now thanks to NCI a small cadre of researchers in centers ranging
from Boston to La Jolla is attempting to discover not only better
treatment options but the holy grail of a cure for CLL. I say a small
cadre because last week I was privileged to attend a CLL State of the
Science meeting at NCI, and a high proportion of the great CLL bench
researcher and clinician from the United States and Europe were there.
They could all fit in one not-too-large room.
Many of these researchers are going forward under the umbrella of
the Consortium itself. It was started last year with an NCI program
project grant of $16.5 million to be shared among nine institutions
over four years. For that we are grateful, but we can all do the math.
That is a humble sum on an annual and institutional basis with which to
do lifesaving work. The program project grant is exactly the same
amount Mrs. Casey spent to buy the site on Foxhall Road here in
Washington for a new residence for our mayors.
To my astonishment, the Consortium is unique. It is a model. It
must succeed and is succeeding. Why is it unique? Because for the first
time in NCI history it brings together that nation's top researchers on
a given type of cancer from different disciplines--genetics, cell
biology, immunology and pharmacology, to conduct an integrated program
of basic and clinical research. It is also unique in that it brings
together many of the great battleships of the cancer wars, ranging from
Dana Farber to Johns Hopkins, to M.D. Anderson to Walter Reed. And they
are all under the leadership of Dr. Thomas Kipps at the University of
California at San Diego. It is not only unique. It is a model in terms
of how we might combat other cancers.
The hope is that cross fertilization among leading research
institutions which might not otherwise work together will generate
life-saving insights, not only about CLL--and this is important--but
about many other types of cancers as well. The interaction is already
generating new opportunities, opportunities that can not be pursued
vigorously at present funding levels. A remarkable CLL Consortium
specialist seated near me at last weeks NCI meeting forgot to bring his
pen. He told me later that he initially thought he would not need it
because he was up on all the latest development. But within the first
few minutes of cutting-edge presentations, he had borrowed a pen and
went on to scribble all morning. There is much that is new and
exciting.
More specifically, more funding is now needed by the Consortium for
a stronger research infrastructure, to support further clinical trials
on at least six new agents, to fund additional institutional
participation, attract additional researchers--particularly in gene
therapy, to support expensive data and tissue flow and to encourage the
kind of breakthroughs that would attract even more support. The
recently developed (and often quite harsh) treatments like Rituxan and
Campath are not enough, although desperate patients welcome them. They
are not a cure, far from it. They have their costs as well as their
benefits. Nevertheless, they show what can be done by NIH, NCI, the CLL
Research Consortium and other academic researchers and the
pharmaceutical companies.
Simply take as an example the tissue sharing done by the
Consortium. Researchers around the country can now secure blood and
tissue samples for CLL research purposes. But the process involved in
freezing fbrzshipment and-assuring tissue quality at the other end is
highly sophisticated and extremely expensive. So is the exchange of
data developed by the Consortium. But it is an absolutely vital
process.
A measure of success in the model Consortium program is leading the
way for other potential collaborative efforts to fight an array of
cancers and other diseases that affect the lives of so many of us in
this room and millions of other Americans every day. But all this will
cost even more money. I believe it is money the American people are
willing to spend.
In conclusion, permit me to quote from Dr. Brian Druker, the
principal investigator on Gleevec when he was asked how it feels to
have made the breakthrough towards a cure for CML. He recently said:
``It's something that is very hard to put into words, and I will
share with you what a senior clinical researcher shared with me the
other day, and he really put it succinctly. And that was, right now its
enjoyable to go to clinic to see our patients being treated with
(Gleevec) in a way he never thought imaginable. Patients are grateful
in a way we never thought imaginable because of the way they feel and
because of the hope that we have restored for the future for them. For
me to hear those sorts of words and to know that this is something I
have dreamed about for my entire career, this is something I have
worked toward, and to actually see it come true is something that I
really just can't put into words, but I can tell you, it just feels
incredibly good.''
Mr. Chairman, if it feels so good to a compassionate doctor like
Brian Druker, who once treated me when I fell ill in Portland, Oregon,
you can imagine how it must feel to patients and their families--to
know that a cure may be in sight and that for now their lives are being
restored to them. Let's make it possible to do the same for CLL and all
other blood disorders.
Thank you very much.
STATEMENT OF HAGOP M. KANTARJIAN, M.D., CHAIRMAN,
LEUKEMIA DEPARTMENT, M.D. ANDERSON CANCER
CENTER
Senator Specter. We turn now our final witness on this
panel, Dr. Hagop Kantarjian, chairman of the Leukemia
Department at M.D. Anderson Cancer Center. He received his B.S.
and M.D. from American University of Beirut in Lebanon. Thank
you for joining us and we look forward to your testimony.
Dr. Kantarjian. Thank you, Senator Specter and Senator
Hutchison, for the opportunity to talk about leukemias. I am
going to be brief, but I would like to include by written
document in the permanent records, if you wish.
Senator Specter. The full statement will be made a part of
the record, without objection.
Dr. Kantarjian. Thank you.
For children and adults, leukemia still presents a major
health problem and it affects about 50,000 individuals in the
United States every year. Thirty years ago, a diagnosis of
leukemia was a death sentence. But today, with the discoveries
and the research, we can offer the hope that we will help most
of these patients and that we can probably cure over half of
these patients.
Aside from the need to cure, treat, and prevent leukemias
ultimately, leukemias are an excellent model to study because
of the accessibility of the leukemic cells so that a lot of the
lessons that we learn from leukemia help other cancers.
How did we improve the cure in leukemia? This was the
result of multiple approaches, including chemotherapy, biologic
modalities, bone marrow transplantation, and most importantly,
the targeted therapies which I will discuss briefly.
But it is important to note that chemotherapy today cures
about 80 percent of children with acute lymphocytic leukemia
and about 40 to 50 percent of adults with acute leukemia. There
are certain acute leukemias which can be treated with only 1
week of chemotherapy, like hairy cell leukemia, or even without
chemotherapy but only using vitamin A analogs or arsenic
trioxide. Of course, transplant, when it is available, cures
about 50 percent of the patients with leukemias and other
hematologic cancers.
But as I mentioned, the greatest progress has happened over
the past 5 years with the targeted therapies, and in simple
terms, leukemias send messages to the outside that identify
them as very specific. So, with developed drugs, which are
called targeted therapies that look for those signals and there
are two kinds which have been very successful: the monoclonal
antibodies, which many of them have been approved by the FDA,
and then the Gleevec, which is really a magic pill which has no
side effects, and based on the research, we think will cure
about half of the patients with chronic myeloid leukemia.
M.D. Anderson from the great State of Texas and many other
institutions have been involved in this research, and this is
made possible only through the granting mechanisms of the NCI
and the NIH. The reason is leukemia is a small market for drug
companies, so they do not usually do the research. We have to
do it, and when there is a lead, they go for that.
But another important point is we have to have a balanced
funding of that research. I personally believe that clinical
research has been neglected, and acceleration of the success
will come through a balanced funding of both the laboratory and
clinical research.
PREPARED STATEMENT
The final question, which I am sure Senator Specter will
ask me, so I will ask it to myself, is when will we cure all
these leukemias. I truly believe from my heart and also from my
mind that based on the base of the discoveries, that we will be
able to cure most, if not all, of the leukemias in next 10
years. Thank you.
[The statement follows:]
Prepared Statement of Hagop M. Kantarjian
BACKGROUND
Leukemias are categorized by the aggressiveness of their course
when untreated (acute versus chronic), and the cell involved (myeloid
versus lymphoid). Thus, we often refer to four major types.
----------------------------------------------------------------------------------------------------------------
Acute Chronic
----------------------------------------------------------------------------------------------------------------
Myeloid Lymphoid Myeloid Lymphoid
----------------------------------------------------------------------------------------------------------------
acute myeloid leukemia or AML........ acute lymphoid leukemia chronic myeloid chronic lymphoid
or ALL. leukemia or CML. leukemia or CLL
----------------------------------------------------------------------------------------------------------------
The overall yearly incidences of leukemias in the USA are:
Approximate
Leukemia yearly incidence
AML............................................................... 8,000
ALL............................................................... 5,000
CML............................................................... 7,000
CLL...............................................................10,000
Another group related to AML myelodysplastic syndrome (MDS) affects
12,000 to 20,000 individuals/year. Thus leukemias affect overall
40,000-50,000 people in the USA.
current status and progress in leukemias
Over the past 20 years, we have made major progress in the
treatment of each of the leukemias. The cure rates in year 2000 for
each leukemia and reasons for progress are shown below.
----------------------------------------------------------------------------------------------------------------
Potential cure
Leukemia (percent) Average survival Treatment
----------------------------------------------------------------------------------------------------------------
Childhood ALL........................ 80..................... NA..................... Combination
chemotherapy.
Adult ALL............................ 40-50.................. NA..................... Same.
Adult AML............................ 20-60.................. NA..................... Same.
acute promyelocytic leukemia..... 70..................... ....................... All trans retinoic acid
arsenic trioxide.
CML.................................. 50 with transplant..... > 7 years.............. Transplantation
Interferon alpha,
Gleevec.
CLL.................................. ....................... 6-8 years.............. Fludarabine, Rituxan.
-hairy cell leukemia............. 80..................... NA..................... chlorodeoxyadenosine.
----------------------------------------------------------------------------------------------------------------
NA = Not applicable.
Major areas of treatment discoveries have included:
(1) new chemotherapy drugs
(2) transplant modifications
(3) agents that differentiate leukemias to normal cells such as
all-transretinoic acid (vitamin A-like drug) and arsenic trioxide
(4) targeted therapies in the form of:
--monoclonal antibodies: Rituxan, campath 1H, Zevalin, Mylotarg,
Bexxar
--small molecules that block signals that stimulate/cause cancer
cells: the best example is Gleevec; others include
angiogenesis inhibitors, (i.e. agents that block vessels
that feed cancers), and others.
WHAT ARE TARGETED THERAPIES
Cancer cells in general, and leukemic cells in particular produce
signals or messages which (1) can cause the cancer/leukemia, or (2)
identify them selectively (e.g. surface proteins). The past five years
have been very exciting in leukemia research because we successfully
developed many monoclonal antibodies that target the surface proteins
on leukemic cells, and also several ``small molecules'' that block the
signals that may cause leukemias.
Several monoclonal antibodies have now been approved by the FDA for
leukemias and are already improving patient prognosis: Rituxan, Campath
1H, Mylotarg. The best example of a ``signal inhibitor'' is STI571 or
Gleevec which blocks the function of protein that causes CML. We
believe this very simple small molecule (Gleevec) which is given by
mouth, and has almost no side effects (unlike chemotherapy) may lead to
the cure of half of all CML patients without requiring transplant. We
would like to develop similar selective targeted therapies for most
leukemias. Research in these areas is progressing very rapidly.
Research in leukemia often cross fertilizes other areas of research in
cancer and serves as a useful model to identify new treatments that
also help other cancers. Thus funding research in leukemia helps
research in other cancer.
FUTURE HOPES, EXPECTATIONS AND NEEDS
Based on the current pace of discoveries, I predict we will be able
to cure most leukemias with treatments that have good tolerance in the
next 10 years.
To accomplish this, funding by the NIH/NCI is crucial to support:
(1) research projects that investigate new chemotherapy agents,
immunologic strategies (e.g. vaccines), targeted therapies, and others.
(2) translational research that translates the laboratory
discoveries into clinical research realities.
(3) clinical research, an often neglected area of grant support,
without which progress will be inhibited. We need to support clinician-
scientists who conduct superior clinical research and make discoveries
in human trials that improve the outcome of leukemias.
a brief glimpse at the leukemia program at m.d. anderson cancer center
Our group at M.D. Anderson includes 15 leukemia specialists who are
probably the best in the world. Our leukemia service treats about 2,000
new leukemia cases per year. This is by far the largest program in the
world with total dedication to curing one disease--leukemia.
Our cumulative expertise is by far superior to any other program in
the world, and we have been responsible for, or associated with most of
the discoveries in leukemia therapies. Our program has been funded to a
significant extent by the NIH and NCI grant support. Such continued
funding mechanisms are vital to the continued success in leukemia
research.
Senator Specter. That is very encouraging. You are right. I
always do ask that question because if you can put something
tangible on the line, it impresses Members of the Senate and
House.
We have been joined by the senior Republican on the full
committee and former chairman. Senator Stevens, would you care
to make a statement or question?
STATEMENT OF SENATOR TED STEVENS
Senator Stevens. I regret I was not here to hear Dr.
Klausner. I had fully intended to be here, Doctor, but we are
working on the supplemental right now, and I have just dropped
by as a fellow cancer survivor, prostate cancer, Mr. Lucchino,
to welcome you all and to tell you of our continued support for
your endeavors. We hope we can get as much money as possible to
meet this medical research schedule. I am not sure how much
money yet there is available, but we will get all there is. Let
us put it that way.
Thank you.
Senator Specter. I might add that Senator Stevens has been
enormously supportive of what this subcommittee has recommended
and has vigorously supported the doubling of funding within 5
years for the NIH. So, we thank you.
We are going to have 4-minute rounds by the members.
Let me address the first question to Mr. Pendleton. You
comment that you are a sufferer of leukemia without any
discernable cure in the offing. How do you feel about a
situation where embryos are available which are going to be
discarded and these embryos can produce stem cells which have
enormous promise for answering and providing a cure for
precisely the kind of ailment which you have? How do you feel
about that?
Mr. Pendleton. Senator, you can imagine that I and many and
I think perhaps most other patients feel extremely strongly
that research must go forward on every front. It is necessary
to save the lives of Americans and to make the lives of
millions of Americans more bearable.
Senator Specter. Mr. Lucchino, the same question. Senator
Gordon Smith of Oregon, a very strong pro-life Senator, has
made the point that it is very different if you have an embryo
in the womb of a woman where there is progress toward the
creation of life, contrasted with a discarded embryo in a dish.
As someone who has suffered from a variety of forms of cancer,
how do you feel about legislation which is now on the books
which prevents the National Institutes of Health from using
Federal funding to extract stem cells from embryos which might
provide a broader range of cures for cancer and other ailments?
Mr. Lucchino. Senator, I echo Mr. Pendleton's observations.
I readily admit that I am deeply biased on this. I hate these
blood diseases so severely that I think that not to avail
ourselves of every opportunity is a terrible tragedy.
Senator Specter. One of the really critical factors about
these hearings is to mobilize public opinion, and if these
embryos were to produce life, I would never propose using the
stem cells for research. But where they are going to be
discarded and you have the positive testimony by the
scientists, it seems to me that the point has to be made again
and again until it resonates through America.
To Drs. Kantarjian and Horning, brief answers. How
important do you think the potential for stem cells are in
curing cancer? Ladies first.
Dr. Horning. Well, as my focus is clinical research, I will
speak from that vantage. I would echo what my co-panelists have
to say from the patients' perspective and from the physician or
clinical researcher perspective. I feel that all leads must be
followed. That is going to take many minds and many methods to
achieve the cure. As we have heard from Dr. Klausner, there are
certain diseases in which the use of embryonic stem cells will
be more needed.
Senator Specter. With all these embryos available, Dr.
Kantarjian, despite that 10-year estimate?
Dr. Kantarjian. Right. I think you have put it very
clearly. I do not think that stem cell research is debated in
the scientific issue. I think it is a political issue because
of its potential association to abortions. But from the
scientific point of view, stem cell research is very important
and discarded embryonic tissue is important for this kind of
research.
Senator Specter. Thank you very much.
Senator Murray.
Senator Murray. Well, thank you very much, Mr. Chairman,
and thank you to all of our panelists for excellent testimony.
I think it was very clear the bottom line is research,
education, and funding, funding, funding. So, I appreciate your
message.
I just have one question. I know we have other panelists,
so we need to move along. That is the same question I asked to
Dr. Klausner earlier. We are debating the Patients' Bill of
Rights and one of the contentious issues is whether or not
patients should have access to clinical trials. Could either
Dr. Kantarjian or Dr. Horning comment on that?
Dr. Kantarjian. I think the only way you can make progress
is through the clinical trials, and it is a false notion that
clinical trials increase the cost. I think clinical trials
reduce the cost because they allow accessibility to high
quality research that will benefit everybody.
Dr. Horning. I agree there are data that indicate that the
cost of care is not increased by clinical trials and studies
show that the quality of care is improved for participants in
clinical trials.
Importantly, clinical trials help us to determine the leads
that are promising, and when we find the ones that are, we move
ahead, and if they are dead ends, then we turn to a different
direction. I think the experience of bone marrow
transplantation in breast cancer is an excellent example of
that.
Senator Murray. Thank you very much. Thank you, Mr.
Chairman.
Senator Specter. Thank you very much, Senator Murray.
Senator Hutchison.
Senator Hutchison. Thank you, Mr. Chairman.
Sometimes I think we need a little definition of terms
here. For you, we have been throwing around markup of a
supplemental, and I wanted to explain to you that the
supplemental is the emergency appropriations bill for the needs
that we do not have available funds for in the rest of this
year for our budget. The markup means we are trying to get the
bill out of committee.
Now I want to ask you a question on definition of terms and
make sure that we are clear on clinical trials. I want you to
define the difference between clinical trials and pure lab
research.
Dr. Kantarjian, I want to thank you for being here from
M.D. Anderson, which is doing such a wonderful job in cancer
research and treatment. I want to ask you to also expand on
your point that much of this research needs to be done through
NCI and NIH because the pharmaceutical companies cannot focus
as much when it is a small number of patients who would use it
in the end. I want you to go forward and tell us in the
clinical trials, if the NCI and NIH funding is helpful in the
clinical trials as much as it could be.
Dr. Kantarjian. Let me define a clinical trial. A clinical
trial is a controlled investigation where we put forward our
best knowledge and we offer it to the patients. So, it is
really not what people refer to as experimentation or a guinea
pig process. There are no guinea pigs. A clinical trial, or an
investigation, offers our best knowledge to the patients. So,
it is a two-way benefit where the patients benefit from the
most advanced knowledge and we benefit from gathering the data
and publishing it. So, clinical trials are very important as
opposed to clinical practice, and they are different from
laboratory research where you are just looking at the basis
mechanisms. You have to translate that knowledge into the
clinic. Remember that if you put all your money in the
laboratory research, you are not going to cure a single patient
and oftentimes the first experience in the first individual
will give us a lot of information.
Senator Hutchison. Do NCI and NIH do enough to help in the
clinical trials? We have been talking about whether insurance
should cover it, but are we doing enough in the research area
in Government or do we need to make changes there?
Dr. Kantarjian. I think we are in the right direction, but
there are two areas which need to be improved. One is the
process where the insurance companies would pay for the
clinical trials, and the second is enough and continuous
funding because, as I mentioned, drug companies look for block
buster drugs, a billion dollar drug. This does not exist in the
leukemias, and this is why the leukemias have been a neglected
entity. In fact, most of the discoveries has been made through
the funding by the NCI and the FDA and academic institutions
and then were taken by the drug companies. So, it is very
important to continue that Federal and State funding to the
leukemia and hematologic cancer research.
Senator Hutchison. Thank you for being here.
Dr. Kantarjian. Thank you.
Senator Specter. Thank you very much, Senator Hutchison.
Senator Mikulski.
Senator Mikulski. Thank you, Mr. Chairman. To all of the
witnesses, thank you for your most poignant and instructive
testimony.
In the interest of time, I am only going to address one
question to Mr. Lucchino. It goes to public education in early
detection. In the bill Senator Hutchison and I are working on--
and she has been the lead architect--we establish a program at
the Centers for Disease Control and Prevention (CDC) and
instruct them to create a public awareness program. Also, I
think everyone testifying will talk about the need for early
detection and screening.
So, let me then get to my question. While we have been
strong fighters for women's health, we are often worried that
men do not go see doctors. They do not get the early detection
and this cuts across all social class lines. My question to
you, because you are really, as the Padre guy and the former
Orioles guy and Edward Bennett Williams law firm, you have
really been with the male culture.
Mr. Lucchino. Is that in the nature of a criticism?
Senator Mikulski. No. An observation.
My question to you is what advice or insights would you
give to really encourage men to go to the doctor and also what
could we have the CDC focus on in terms of the kinds of
examinations needed or getting men to go in for the early
detection? Yours was detected through an annual health exam.
Quite frankly, most guys do not go for it.
Mr. Lucchino. Right. Well, I consider myself reasonably
well informed and well educated, but when I was diagnosed with
lymphoma, I had no idea what lymphoma was. At that time, I had
no idea what a prostate was. I think there is a crying need for
the kind of public awareness that you are talking about.
How to go about it is a multi-faceted question. Certainly
events like this hearing today go a long way. I have read more
about blood cancers in the last 3 days than I have read in my
lifetime. I think that that has a lot to do with Geraldine
Ferraro and it has a lot to do with the focus of this committee
today. I think that what the baseball world is doing with
prostate cancer is an example of what the private sector can
and must do. What the Cure for Lymphoma Foundation does is
another example of what the private foundation can do. We must
talk about it a lot. We must talk about it publicly, privately
and certainly with the media. And men need to talk about it as
much as possible.
Senator Mikulski. Do you think men would be influenced by
sports figures and through public service announcements?
Mr. Lucchino. I do. I think there is no doubt about that.
The cyclist, Lance Armstrong; golfer, Arnold Palmer; hockey
player, Mario Lemieux; former Oriole, Eric Davis. I think the
experience of these people and the public nature of their
experience, talking about it, coming forward, and making the
world aware that there is life after a cancer diagnosis is
enormously important to the public awareness you are talking
about.
Senator Mikulski. Well, thank you. Thank you, Mr. Chairman,
and to all the panel and to those who, if we had time, ought to
be on the panel, the other survivors, thank you.
Senator Specter. Thank you very much, Senator Mikulski, and
thank you very much.
We will now turn to the next panel. Geraldine Ferraro, Dr.
Kenneth Anderson, Dr. John Holaday, and Ms. Kathy Giusti.
We will begin with the Honorable Geraldine Ferraro, who has
had an extraordinary career. A lawyer by profession, elected to
the House of Representatives in 1978, and then an historical
candidacy for the Vice Presidency of the United States with
Vice President Mondale in 1984. I join Senator Kay Bailey
Hutchison, Congresswoman Ferraro, in praising you for your
courage in coming forward.
Ms. Ferraro. Thank you.
Senator Specter. It carries a lot of weight when people see
someone of your stature who is willing to come forward, and
also if it can happen to Geraldine Ferraro, it can happen to
anybody. We need all of the public support we can get to push
forward the funding and the stem cell research, et cetera. So,
thank you for joining us and the floor is yours.
STATEMENT OF GERALDINE FERRARO, FORMER MEMBER OF
CONGRESS FROM NEW YORK
Ms. Ferraro. Thank you, Senator, and thank you for having
this hearing. I want to thank Senator Harkin and thank you,
Senator Hutchison, for helping make it happen, and my two
buddies, Senator Mikulski and Senator Murray, for being here. I
appreciate it.
I am all too aware of how many things there are to do when
you are in session and how little time there is to do them all.
So, I am particularly grateful for your allowing us to appear
before you to discuss and issue which is, to some of us here, a
matter of life and death.
Several months ago I was at home watching the news and saw
our former colleague, Joe Moakley, at his press conference
disclosing that he had been diagnosed with a blood cancer,
leukemia, which is neither curable nor treatable and announcing
that he would not seek reelection. My heart went out to him in
part because he was such a terrific person who really loved the
Congress, and his announcement was so terribly final. But also
because I knew what he was going through emotionally dealing
with this disease. In December of 1998, I too was diagnosed
with a blood cancer, multiple myeloma, which is also not
curable. Let me hasten to add, however, that unlike Joe's
situation, at least for the present, my cancer is treatable.
I have chosen not to be public about my health until now.
That is one of the benefits of losing an election.
You can keep your private life private. But I am here
because I want to make sure that the public got to know about
multiple myeloma and I wanted to point out to you just how
important research dollars are to dealing with this disease.
Let me start by saying I am a very lucky woman. First of
all, I have the best doctors caring for me. It is because of
one of those doctors, Ronald MacKenzie, my internist, that I
was diagnosed very early. I had gone for my annual checkup and
he noticed in looking over my blood test results that my white
blood count was slightly elevated. He went back and checked my
previous years' records and saw that there was a steady but
slow progression upward of the white cell count over the years.
He called me and said he wanted to see me and that he was
sending my blood out for additional tests because it seemed
that I had either leukemia, lymphoma, or multiple myeloma.
I must say I was a bit taken aback. I did not even know
what multiple myeloma was. I had never heard of it. Dr.
MacKenzie explained that it was a blood cancer that attacks the
bones. Most people do not find out that they have it until a
symptom appears that needs explanation, like aching or broken
bones. And I had no symptoms.
My initial reaction was thank God it is me and not one of
my children. As much as we want to believe that we are
indispensable to our families, my children are all grown and
quite independent. But they are also married and they have
little children of their own who most definitely do need them.
My second reaction was: Why cancer? That is not a disease
that is in my family. We are big on strokes and heart attacks.
Even my mother who smoked died of emphysema, not lung
cancer. So, how did I get multiple myeloma? Was it the
environment? Was it stress? And we all know I have had a little
of that over the years. Was there some hidden genetic
disposition to the disease, and if so, can we check my children
and grandchildren to be sure I have not passed that cancer gene
on to them? And going beyond me, what is it that make African
Americans almost two and a half times more likely than
Caucasians to come down with this disease? Why is it that
multiple myeloma historically manifests itself in people who
are older? Hopefully, future research will be able to answer
all of those questions.
When we left Dr. MacKenzie that day, we were feeling pretty
down. But the holidays were fast approaching, and after seeing
John's devastation on hearing the news, I just did not have the
heart to tell my kids until after Christmas. But once the
holidays were behind us, we told them, and then we went to see
my second wonderful doctor, Jeffrey Teppler, who is an
oncologist.
Before I go on, I want to point out that I keep using the
term ``we.'' That is not the royal ``we.'' That is my husband
John Zaccaro and me. We have been best friends since college.
Next month we will be married for 41 years. We totally enjoy
each other's company but professionally we have led rather
independent lives. Since my diagnosis, however, John drops
everything at the office to drive me to the doctor, to sit with
me for 2 hours at the hospital when I am getting an infusion,
to fly to Boston to meet with my third wonderful doctor, Ken
Anderson, from whom you will hear shortly. And as a matter of
fact, my husband is here today with my eldest daughter Donna.
But back to Dr. Teppler. When I was first diagnosed, my
cancer was inactive. No protein showed in my blood, none in my
urine. So, Dr. Teppler took rather frequent bone marrow samples
and did blood and urine tests on a monthly basis. And I started
monthly infusions of a bone-strengthening drug called
pamidronate.
In June of last year, he called me and told me that the
cancer had become active and that he had spoken with Dr.
Anderson, whom I had met shortly after diagnosis, and they
agreed that I should start taking steroids.
Now, I thought I was going to be able to hit the golf ball
further, swim faster, run like the wind once I got on steroids.
Unfortunately, this type of steroid has none of the
beneficial effects that the steroids that athletes take. It did
deal with the cancer, though it was mood altering and made me
terribly irritable. It also made me slightly puffy which was
not all that bad since all of my wrinkles temporarily
disappeared without the cost or inconvenience of a face lift.
I continued taking the steroids through the summer and
early fall and they worked beautifully, reducing the cancer
protein, until November. And then I plateaued. It was time to
go to Dr. Anderson to discuss stem cell transplants.
Though I was not happy about it, I was resigned to the fact
that I would need the procedure since I had been told it was my
next step in treating the disease. And without treatment, quite
simply I will die. I was told the stem cell transplant would
involve 3 weeks in the hospital, that I would be getting
massive doses of chemotherapy, followed by radiation, that my
immune system would be totally destroyed and that I would need
approximately 3 months at home to recuperate.
I was worried about how I would deal with that amount of
time out of circulation. I worried about my business, my
family, and to be quite frank, I worried about myself.
The one thing I was not worried about was the cost. I am
told the price tag for the procedure is $50,000 to $100,000. I
am now eligible for Medicare and Medicare covers the procedure.
But even if it did not, my insurance does, and if my insurance
did not cover it, I could still afford to pay for the procedure
myself if I need it. But what about those who cannot? What
about those who do not have health care coverage? I guess those
are two questions that will properly be answered at a future
hearing on health care legislation instead of here today.
Dr. Anderson went through the whole process with John, my
youngest daughter Laura, and me. And then he said that several
of his patients had opted to take thalidomide as an alternative
to having the stem cell procedure done. I was intrigued. I was
having babies in the 1960's when thalidomide was making
headlines as a dreaded pill that, when taken by pregnant women,
caused severe damage to fetuses. Children were being born with
all kinds of deformities. But what destroyed healthy growth
then was now being used to prevent cancer growth. Dr. Anderson
described for us just how thalidomide works, which I am sure he
will do for you, and when we heard that it had the potential
for treating the disease with minimal side effects, that if it
did not work, we were not precluded from doing the stem cell
transplant in the future, we opted to try thalidomide.
I have been taking thalidomide since November. It is
working. Once a month, I still go for an infusion, and once a
month I get blood and urine tests. Then I wait for three very
long days until my test comes back to hear from Dr. Teppler. Am
I still doing well? Have the cancer cells figured out a way to
fight the thalidomide? And if they have, what if any option do
I have before I deal with a stem cell transplant?
I do not expect you to answer those questions, Senators.
Those I reserve for Dr. Anderson. And I have such confidence in
him and the other researchers who are dealing with multiple
myeloma that I know they will have the next step ready for me
when I need to take it.
But they need you and your colleagues in the Congress to
help. They need more awareness and attention being paid to
blood cancers so that people will test early and be diagnosed
earlier. They need research dollars to continue to search for
new treatments and a cure, and they need faster approval by the
FDA of new drugs.
Pharmaceutical companies have been slow to underwrite
research for multiple myeloma because each different blood
cancer requires different treatment. What is good for leukemia
or lymphoma will not help me. So, if you take each of the blood
cancers separately, we are talking about orphan drugs since
there just are not enough potential users of each to make it
financially worthwhile for the pharmaceutical companies.
On the other hand, this is still a huge problem for this
country, for if we lump together leukemia, lymphoma, and
multiple myeloma, last year's figures show that the mortality
rate for blood cancers is second only to lung cancer, 20
percent higher than colon blood, one-third higher than breast
cancer, and almost twice as high as prostate cancer. Those
diseases receive far more attention and far more funding.
Now I am not suggesting for 1 minute that attention or
funding to the other diseases be reduced. My husband is a
survivor of colon cancer because of early detection. I nagged
my two older children until they got a colonoscopy, and I will
get up on a soapbox and tell the world how important it is to
be tested to detect that disease because it is curable. I also
served when I was in the House and even after on a breast
cancer task force, and I have spoken out and walked more than
once to raise money for that cause which I will continue to do.
But what I am suggesting is that blood cancers are a serious
and costly health concern and they too need our attention and
funding.
Multiple myeloma is hitting a lot of elderly, and though I
wince when I refer to myself that way, I am not an unusual
candidate for this disease. But just think about the
consequence of that demographic. I mentioned before that if I
need a stem cell transplant, it will cost between $50,000 and
$100,000 and that Medicare will pay for it. Instead, my
insurance company is paying $264 a month for a prescription of
thalidomide. A year ago, that cheaper option of thalidomide was
not available. Research made the difference. Now, what happens
when thalidomide stops working, and I go month to month not
knowing when Dr. Teppler will call and tell me that? Will Dr.
Anderson be able to give me some new drug, or will he have to
tell me that it is in clinicals and he is not quite sure when
it will be approved, so it is time for a transplant? It almost
goes without saying that combining investment and research with
faster Government approval of drugs is a cost effective way of
dealing with the expense of this disease to our health care
system.
I told you when I started that I am a lucky woman. I have
great doctors, an early diagnosis, and up-to-the-minute
treatment that works. But cancer does not only eat at your
body. It is a disease that can destroy you both emotionally and
psychologically. I am blessed with a family that is always
there to boost me up. In addition to their constant concern for
me, my daughter Donna has taken her business and media
experience and put it to work to help the Multiple Myeloma
Research Foundation raise awareness and money. My son John, who
is a lawyer, has filled in and taken over the headaches of
John's business so his dad can be with me. Laura is the doctor
who keeps an eye on my test results and asks the questions I
forget to ask and answers the ones that I am too embarrassed to
ask. My four grandbabies give me hugs and kisses and a
thousands reasons a day I want to fight this thing. They and
John, of course, and a few close friends--and Barbara Mikulski
was one of the people I confided in almost immediately after I
found out that I had this--have given me the emotional support
that all of us need when we are slapped in the face with our
mortality. Living in New York City, I am never quite sure when
I run into a street to hail a cab that I am going to live long
enough to ride in it.
But hearing that you have a disease that is incurable with
an average life span of just 3 years does make one stop and
notice.
I expect that with my trio of medical miracle workers, with
the love of my family and friends, with my mother and all the
nuns who took care of me a as little girl praying for me, that
I will be around at least until 2010 so that I can take
advantage of President Bush's elimination of the inheritance
tax--hopefully even after that so that I can be invited to the
inauguration of the first female President of the United
States, Senators.
PREPARED STATEMENT
In the meantime, however, I, as well as every other
multiple myeloma patient, am hoping that you, Senators, will
provide help to these doctors so they can continue their
research and eventually find a cure to this disease.
Again, thank you, Mr. Chairman, Senator Specter, Senator
Hutchison, Senator Murray, Senator Mikulski.
[The statement follows:]
Prepared Statement of Geraldine A. Ferraro
I want to begin by thanking you, Mr. Chairman, and Senator Spector
for holding this hearing and Senator Hutchinson for helping to make it
happen. As a former member, I am all too aware of how many things there
are to do when you are in session and how little time there is to do
them all, so I am particularly grateful for your allowing us to appear
before you to discuss an issue which is, to some of us here, a matter
of life and death.
Several months ago I was at home watching the news and saw our
former colleague, Joe Moakley at his press conference disclosing that
he had been diagnosed with a blood cancer, leukemia, which was neither
curable nor treatable and announcing that he would not seek reelection.
My heart went out to him in part because he was such a terrific person
who really loved the Congress and his announcement was so terribly
final. But also because I knew what he was going through emotionally
dealing with his illness. In December of 1998, I too was diagnosed with
a blood cancer, multiple myeloma, which is also not curable. Let me
hasten to add, however, that unlike Joe's situation at least for the
present, my cancer is treatable.
I have chosen not to be public about my health until now. That's
one of the benefits of losing an election, you can keep your private
life private. But I am here because I wanted to make sure that the
public got to know about multiple myeloma and I wanted to point out to
you just how important research dollars are to dealing with this
disease.
Let me start by saying I am a very lucky woman.
First of all, I have the best doctors caring for me.
It is because of one of those doctors, Ronald MacKenzie, my
internist, that I was diagnosed very early. I had gone for my annual
checkup and he noticed in looking over my blood test results, that my
white blood count was slightly elevated. He went back and checked my
previous years records and saw that there was a steady but slow
progression upward of the white cell count over the years. He called me
and said he wanted to see me and that he was sending my blood out for
additional tests because it seemed that I had either leukemia, lymphoma
or multiple myeloma.
I must say I was a bit taken aback. I didn't even know what
multiple myeloma was, I had never heard of it. Dr. MacKenzie explained
that it was a blood cancer that attacks the bones. Most people don't
find out that they have it until a symptom appears that needs
explanation--like aching or broken bones. I had no symptoms.
My initial reaction was: Thank God it's me and not one of my
children. As much as we want to believe that we are indispensable to
our families, my children are all grown and quite independent. But they
are also married and they have little children of their own who most
definitely do need them.
My second reaction was: Why cancer? That's not a disease that's in
my family. We're big on strokes and heart attacks. Even my mother who
smoked, died of emphysema, not lung cancer. So how did I get multiple
myeloma? Was it the environment? Was it stress? (And we all know I've
had a little of that over the years.) Was there some hidden genetic
disposition to the disease? And if so, can we check my children and
grandchildren to be sure I haven't passed that cancer gene on to them?
And going ``beyond me--What is it that makes African Americans almost
two and a half times more likely than Caucasians to come down with this
disease? Why is it that multiple myeloma historically manifests itself
in people who are older? Hopefully, future research will be able to
answer all of those questions.
When we left Dr. MacKenzie that day, we were feeling pretty down.
But the holidays were fast approaching and after seeing John's
devastation on hearing the news, I just didn't have the heart to tell
my kids until after Christmas. But once the holidays were behind us, we
told them and then we went to see my second wonderful doctor, Jeffrey
Teppler who is an oncologist.
Before I go on, I want to point out that I keep using the term
``we''. That is not the royal we. The ``we'' is my husband John and me.
We have been best friends since college and we've been married for 41
years. We totally enjoy each other's company but professionally we've
led rather independent lives. Since my diagnosis, however, John drops
everything at the office to drive me to the doctor, to sit with me for
two hours at the hospital when I'm getting an infusion, to fly to
Boston to meet with our third wonderful doctor, Ken Anderson whom you
will hear from shortly and as a matter of fact, my husband is here
today with my eldest daughter, Donna.
But back to Dr. Teppler. When I was first diagnosed, my cancer was
inactive. No protein showed in my blood, none in my urine. So Dr.
Teppler took rather frequent bone marrow samples and did blood and
urine tests on a monthly basis and I started monthly infusions of a
bone-strengthening drug called pamidronate. In June of last year, he
called me and told me that the cancer had become active and that he had
spoken with Dr. Anderson, whom I had met shortly after diagnosis, and
they agreed that I should start using steroids.
Now I thought I was going to be able to hit the golf ball farther,
swim faster, and run like the wind once I got on steroids.
Unfortunately, this type of steroid has none of the beneficial effects
of the steroids that athletes take. It did deal with the cancer though
it was mood altering and made me terribly irritable. It also made me
slightly puffy which wasn't all that bad since all of my wrinkles
temporarily disappeared without the cost or inconvenience of a
facelift!
I continued taking the steroids through the summer and early fall
and they worked beautifully, reducing the cancer protein. Until
November. Then I plateaued. It was time to go back to Dr. Anderson to
discuss stem cell transplants.
Though I wasn't happy about it, I was resigned to the fact that I
would need the procedure since I had been told it was my next step in
treating the disease. And without treatment, quite simply, I will die.
I was told a stem cell transplant would involve three weeks in the
hospital, that I would be getting massive doses of chemotherapy
followed by radiation, that my immune system would be totally destroyed
and that I would need approximately three months at home to recuperate.
I was worried about how I would deal with that amount of time out of
circulation. I worried about my business, my family and to be quite
frank, myself. The one thing I wasn't worried about was the cost. I am
told the price tag for the procedure is $50,000 to $100,000. I am now
eligible for Medicare and Medicare covers the procedure. But even if it
didn't, my insurance does. And if my insurance didn't cover it, I could
still afford to pay for the procedure myself if I need it. But what
about those who can't? What about those you don't have health care
coverage? I guess those are two questions that will properly be
answered at a future hearing on health care legislation instead of here
today.
Dr. Anderson went through the whole process with John, my youngest
daughter Laura and me. And then he said that several of his patients
had opted to take thalidomide as an alternative to having the stem cell
procedure done. I was intrigued. I was having babies in the 60's when
thalidomide was making headlines as a dreaded pill that when taken by
pregnant women caused severe damage to fetuses. Children were being
born with all kinds of deformities. But what destroyed healthy growth
then was now being used to prevent cancer growth. Dr. Anderson
described for us just how thalidomide works, which I'm sure he will
also do for you, and when we heard that it had the potential for
treating the disease with minimal side effects, that if it didn't work
we were not precluded from doing the stem cell transplant in the
future, we opted to try thalidomide.
I have been taking thalidomide since November. It's working. Once a
month I still go for my infusion and once a month I get blood and urine
tests. Then I wait the long three days until my test comes back to hear
from Dr. Teppler. Am I still doing well? Have the cancer cells figured
out a way to fight the thalidomide? And if they have, what if any
option do I have before I deal with a stem cell transplant?
I don't expect you to answer those questions, Senators, those I
reserve for Dr. Anderson. And I have such confidence in him and the
other researchers who are dealing with multiple myeloma that I know
they will have a next step ready for me when I need to take it. But
they need you and your colleagues in the Congress to help. They need
more awareness and attention being paid to blood cancers so that people
will test early and be diagnosed earlier; they need research dollars to
continue to search for new treatments and a cure; and they need faster
approval by the FDA of new drugs.
Pharmaceutical companies have been slow to underwrite research for
multiple myeloma because each different blood cancer requires different
treatment. What's good for leukemia or lymphoma will not help me. So if
you take each of the blood cancers separately, we're talking about
orphan drugs since there aren't enough potential users of each to make
it financially worthwhile for the pharmaceutical companies.
On the other hand, this is still a huge problem for this country
for if we lump leukemia, lymphoma and multiple myeloma together, last
year's figures show that the mortality rate for blood cancers is second
only to lung cancer, 20 percent higher than colon cancer, one third
higher than breast cancer and almost twice as high as prostate cancer.
Those diseases receive far more attention and far more funding. Now I'm
not suggesting for one minute that attention or funding to the other
diseases be reduced. My husband is a survivor of colon cancer because
of early detection, I nagged my two older children until they got a
colonoscopy and I will get up on a soap box and tell the world how
important it is to be tested to detect that disease because it is
curable. I also served when I was in the House and even after on a
Breast Cancer Task Force and I have spoken out and walked more than
once to raise money for that cause which I will continue to do. But
what I am suggesting is that blood cancers are a serious and costly
health concern and they too need our attention and funding.
Multiple Myeloma is hitting a lot of elderly and though I wince
when I refer to myself that way, I'm not an unusual candidate for this
disease. But just think about the consequence of that demographic. I
mentioned before that if I need a stem cell transplant it will cost
between 50 and 100 thousand dollars and that Medicare will pay for it.
Instead, my insurance company is paying $264.00 a month for a
prescription for thalidomide. A year ago that cheaper option of
thalidomide was not available. Research made the difference. Now what
happens when thalidomide stops working, and I go month to month not
knowing when Dr. Teppler will call and tell me that. Will Dr. Anderson
be able to give me some new drug? Or will he have to tell me that it's
in clinical trials and he's not quite sure when it will be approved so
it's time for a transplant. It almost goes without saying that
combining investment in research with faster government approval of
drugs is obviously a cost effective way of dealing with the expense of
this disease to our health care system.
I told you when I started that I am a lucky woman. I have great
doctors, an early diagnosis and up to the minute treatment that works.
But cancer doesn't only eat at your body; it is a disease that can
destroy you both emotionally and psychologically. I am blessed with a
family that is always there to boost me up. In addition to their
constant concern for me, my daughter Donna has taken her business and
media experience and put it to work to help the Multiple Myeloma
Research Foundation raise awareness and money. My son John who is a
lawyer has filled in and taken over the headaches of John's business so
that his dad can be with me. Laura is the doctor who keeps an eye on my
test results and asks the questions I forget to ask and answers the
ones that I'm too embarrassed to ask. My four grandbabies give me hugs
and kisses and a thousand reasons a day to want to fight this thing.
They, and John of course, and a few close friends in whom I confided
have given me the emotional support that all of us need when we're
slapped in the face with our mortality. Living in New York City, I'm
never quite sure when I run into a street to hail a cab that I'm going
to live long enough to ride in it, but hearing that you have a disease
that is incurable with an average lifespan of just three years, does
make one stop and notice.
I expect that with my trio of medical miracle workers, with the
love of my family and friends, and with my mother and all of the nuns
who took care of me as a little girl praying for me, that I will be
around at least until 2010 so that I can take advantage of President
Bush's elimination of the inheritance tax and hopefully even after, so
that I can be invited to the inauguration of the first female President
of the United States. In the meantime, however, I, as well as every
other multiple myeloma patient, am hoping that you, Senators, will
provide help to these doctors so they can continue their research and
eventually find a cure to this disease.
Again, thank you, Mr. Chairman and Senator Spector for holding this
hearing.
Senator Specter. Thank you very much. We very much
appreciate your coming forward and the quality of your
testimony. We are pleased that you used this occasion to
announce your candidacy for the presidency.
Some may have noticed that the red light was on a little
longer than usual. The prerogative of the chair is to allow
that when you have ex-vice presidential candidates who are
women.
Ms. Ferraro. I appreciate that, Senator. Thank you.
Senator Specter. I am going to waive my 4 minutes to make
up for most of the extra time.
Senator Murray has a commitment and wanted to make just one
brief comment before excusing herself. Senator Murray.
Senator Murray. Thank you, Mr. Chairman, for accommodating
me.
Ms. Ferraro, I just want to thank you. You have been a role
model for so many women who are in politics, I being one of
them. Watching you run for Vice President was an inspiration to
many of us, and I know to many, many young women in this
country still today who now see politics as something they can
do. I would not be sitting on this committee in this place
without people like you who paved the way.
You are doing it again with your courage and your humor,
enlightening all of us about how we need to take on another
little issue, blood cancers. And I just want to thank you so
much for all you have done for so many of us. Thank you very
much.
Senator Specter. Thank you, Senator Murray.
STATEMENT OF KATHRYN E. GIUSTI, PRESIDENT, MULTIPLE
MYELOMA RESEARCH FOUNDATION
Senator Specter. We now turn to Ms. Kathy Giusti, who
founded the Multiple Myeloma Research Foundation in 1996 after
being diagnosed with the ailment. She brings 16 years of
experience as a pharmaceutical executive to her role as
President of the foundation. Thank you for joining us, and we
look forward to your testimony.
Ms. Giusti. Thank you so much, Mr. Chairman and Senator
Hutchison.
My name is Kathy Giusti. I am a multiple myeloma patient,
and I am also president of the Multiple Myeloma Research
Foundation. I just want to thank you for your support of blood
cancers.
I was, indeed, diagnosed with myeloma in 1996 at the time I
was 37, a wife, the mother of a 1-year-old little girl named
Nicole, and I was also in the height of my career as the
highest ranked woman executive at G.D. Searle Pharmaceuticals
in Chicago.
When I was diagnosed, I heard the same statistics that
Geraldine did. I heard that multiple myeloma has no cure, and I
heard on average multiple myeloma patients live about 3 years.
So, of course, I transferred that into my own life, and what I
realized was I would die before my 40th birthday and I would
die before I ever saw my little girl go to kindergarten.
I really could not believe then that a cancer existed that
had absolutely no cure, but I can tell you that my experience
in the pharmaceutical industry helped me to understand why.
With 14,000 patients diagnosed with myeloma each year, it is
really hard to make myeloma a top priority by pharmaceutical
companies. When you compare the return on investment for
myeloma with other cancers such as breast cancer or prostate
cancer, it does not compare. So, when I kept searching every
annual report looking for a new drug in the pipeline in 1996, I
was pretty devastated.
I think for me one statistic said it all. Basically it was
the fact that 28 percent of myeloma patients will be alive 5
years after they are diagnosed, and I compared that to the 90
percent survival that we now see with breast cancer and
prostate cancer. So, it was obvious. Multiple myeloma has been
neglected for decades.
So, I resigned from my career in the pharmaceutical
industry and dedicated my time to trying to raise money for
multiple myeloma research. I founded the foundation with my
twin sister, Karen Andrews, who is an attorney, and basically
what our foundation does is we serve as a venture capital
company raising money for early myeloma research, making sure
we validate the best ideas and then we turn them over to the
pharmaceutical companies and the NCI to move them forward.
In 3 short years, we have raised over $10 million. We have
funded over $8 million in myeloma research grants. Over 75
percent of the grants we fund have been published or presented.
I think the true results of what we have done, stem cell
transplants are now safer, patients are enrolling in new
vaccine trials, and we are helping to pay to understand why
thalidomide is working for patients like Geraldine Ferraro.
The MMRF is just one of several private foundations funding
myeloma research. I am joined here today by the International
Myeloma Foundation, by the Leukemia Society, the McCarty
Foundation, and together we will fund between $10 million and
$15 million in myeloma research. The NCI will fund about $18
million. So, you are seeing one of the highest ratios of
private to public sector funding in oncology.
Now I can tell you that Geraldine Ferraro and I are not
your typical multiple myeloma patients. We both sit here before
you looking perfectly healthy and living as active lives as we
can. But running the foundation, my job is to talk to hundreds
of patients every month who are dying, who are facing
excruciating pain, severe anemia, and who are living very
difficult lives.
PREPARED STATEMENT
So, I urge you to work with us to make sure that the PRG
priorities are implemented. I know that I will dedicate
whatever time Dr. Klausner needs me to to turn those PRG
priorities into a good business plan, and I know Geraldine and
her daughter Donna will help me as well. So, I ask you to be
part of our team and help move the progress forward.
Thank you.
[The statement follows:]
Prepared Statement of Kathryn E. Giusti
Mr. Chairman, my name is Kathy Giusti. I am a multiple myeloma
patient and President of the Multiple Myeloma Research Foundation
(MMRF). I am pleased to appear here today and thank you and the
Committee for your commitment to the issues that surround blood
cancers.
I was diagnosed with multiple myeloma in 1996. I was 37, a wife,
the mother of a one year old little girl. I was also at the height of
my career in the pharmaceutical industry-the most senior female
executive at G.D. Searle in Chicago.
I heard the same statistics that Congresswoman Ferraro did.
Multiple myeloma has no cure. Multiple myeloma patients live on
average, three years. I quickly put the doctor's words in real terms. I
would die before my 40th birthday. I would die before seeing my little
girl go to kindergarten.
I could not believe a cancer existed that had absolutely no cure,
but my experience in industry helped me understand why. With 14,000
Americans diagnosed with multiple myeloma each year, multiple myeloma
could not be a priority for the pharmaceutical industry. The return on
investment for myeloma could never compare with the return on more
prevalent forms of cancer such as breast and prostate cancer. I read
every pharmaceutical journal searching for new compounds in the
pipeline for myeloma. I found none. I contacted the National Cancer
Institute (NCI). But with so little awareness, the NCI was investing
just 12 million dollars in myeloma that year.
One statistic said it all . . . only 28 percent of myeloma patients
would be alive five years after diagnosis compared with the 90 percent
five-year survival seen in breast and prostate cancer and the 62
percent survival for all cancers combined.
It seemed clear to me that myeloma had been neglected for decades.
In 1997, I resigned from my career in the pharmaceutical industry and
with my twin sister Karen Andrews, an attorney, founded the MMRF with
one goal in mind-to fund research. We knew the MMRF could act as a
venture capital firm by funding early myeloma research and validating
new ideas. The pharmaceutical industry and NCI could then take the most
promising ideas and move them forward. In three short years, we've made
tremendous progress. The MMRF has raised over ten million dollars. We
have committed eight million dollars to research grants and research
grants with the remaining funds supporting education. Over 75 percent
of the grants we have funded have been published or presented at major
medical meetings.
The result of our efforts? Stem cell transplants are safer and more
effective than ever before. New vaccine trials are enrolling patients.
We are learning why thalidomide and proteasome inhibitors are working.
Our patient and physician outreach is expediting clinical trials.
The MMRF is one of several groups in the private sector raising
funds for myeloma research. Together with the Leukemia and Lymphoma
Society, the McCarty Foundation, and the International Myeloma
Foundation, we will fund ten million dollars in myeloma research this
year alone. The NCI will distribute approximately $18 million in funds.
This is one of the highest ratios of private to public support seen in
the cancer field.
How can you help us keep this momentum going? How can you help the
700,000 patients suffering with blood cancers today? You can make the
Progress Review Group priorities a reality. Right now, we have a list
of priorities that will reduce the time it takes to bring new compounds
to market from the current 7.2 years to the 2 years we saw with
Gleevec. That list must now be developed and quantified in terms of
manpower, time and funding. We need a clear action plan by year-end.
Why do we have this sense of urgency? Because this year alone,
60,000 Americans will die from blood cancers, second only to lung
cancer. We have promising compounds in the clinic. We need to get them
to the bedside . . . quickly.
I am one of the lucky ones. I have lived five years with myeloma.
In those years, I have celebrated my 40th birthday, watched my daughter
Nicole start kindergarten and first grade and was blessed with a son
named David. But I am not a typical myeloma patient. The many friends I
have met through this illness I have also lost. The many funerals I
attend are a constant reminder that while we have come so far . . . we
are not yet there. I urge you to help us implement the PRG priorities
quickly. Your efforts will bring new treatments to Congresswoman
Ferraro and the hundreds of patients you see here today. And when the
inevitable day comes for my husband and me to tell our young children
mommy has cancer, we can also tell them it's ok, mom has a fighting
chance. Thank you.
Senator Specter. Thank you very much for your testimony,
Ms. Giusti.
STATEMENT OF KENNETH C. ANDERSON, M.D., PROFESSOR OF
MEDICINE, HARVARD MEDICAL SCHOOL
Senator Specter. We turn now to Dr. Kenneth Anderson,
Professor of Medicine at Harvard Medical School and Medical
Director of the Kraft Family Donor Center. He is a member of
the Department of Adult Oncology at Dana-Farber Cancer
Institute. Thank you for joining us, Dr. Anderson, and we look
forward to your testimony.
Dr. Anderson. Thank you very much. It is a pleasure to be
here and I thank you all for your consideration and support of
the blood cancers, illustrated here for us today.
As was said, I am a professor of medicine at Dana-Farber
Cancer Institute and also a Doris Duke Distinguished Clinical
Research Scientist, which means plainly I am committed to
developing new treatments in the laboratory to get to the
bedside for blood cancers.
I focus in particular on multiple myeloma. It is 1 percent
of all cancers. It accounts for 2 percent of all cancer deaths.
Some 14,000 new Americans get it every year, 50,000 total are
affected, and 11,200 individuals died last year of myeloma.
What does it do? Myeloma is the accumulation of these
abnormal tumor plasma cells in the bone marrow. Patients get
infections, bleeding, and they get fractures of their bones
because of thinning of the bone, which precludes just simple
activities of daily life. They also get high blood calciums,
renal failure, and devastating nerve damage.
What can we do about it? We can treat it with conventional
therapy to extend the average survival to 3 to 4 years. High
dose therapy and stem cell transplant can modestly improve
that, perhaps to 4 to 5 years. Unfortunately and tragically, we
cannot cure it.
There is very great reason for promise and optimism. You
have already heard of the novel use of thalidomide to treat
myeloma. The novel concept is it not only kills the tumor cell
directly, but it acts in the bone marrow neighborhood in a way
to make it impossible for the myeloma cell to grow and live
there. You have heard beautiful testimony earlier this morning
about Gleevec, which specifically is a targeted drug to inhibit
the protein that causes chronic myelocytic leukemia. I call
these designer drugs, and in myeloma we have such drugs coming
that will either blow the fuse on the growth circuit or turn on
the death circuit in myeloma cells.
Finally, there is that strategy based on vaccines which
will stimulate the patient's own immune system to reject
myeloma, just like the natural immunity clears an infection.
You heard nicely from Dr. Klausner earlier about the
Progress Review Group process in blood cancers that has
recently concluded. One important priority that was identified
was, in fact, an initiative, a collaboration between academia,
Government, industry, and patients, to shorten the time, which
is now 5 to 10 years, down to 2 years that it takes to get a
novel compound into general clinical practice.
PREPARED STATEMENT
I know that you have all been inspired, as have I, this
morning by the courage that has been demonstrated in the face
of incredible adversity by Geraldine Ferraro, by Kathy Giusti,
by Alan Bailey, and by so many other patients who are in this
room who have currently incurable diseases. The Progress Review
Group process has laid out a road map for us to make a
difference in the next 5 years. If we fail to do that, we will
be condemning patients with blood cancers to needless pain,
suffering, and premature death. In contrast, if you partner
with us, we are now poised to make a huge difference in
prolonging the overall survival and quality of life for
patients with blood cancers worldwide.
[The statement follows:]
Prepared Statement of Kenneth C. Anderson
Good morning. I am Ken Anderson, M.D., a Professor of Medicine at
Harvard Medical School and Dana-Farber Cancer Institute in Boston, and
I thank you most sincerely for the chance to speak here today. I am
also pleased to be here as a Doris Duke Distinguished Clinical Research
Scientist; a member of the Boards of Directors and Scientific Advisors
of the Multiple Myeloma Research Foundation and the International
Myeloma Foundation; as chairman of the National Comprehensive Cancer
Center Network Myeloma Guidelines Panel; as a member of the Medical and
Scientific Committee of the Leukemia & Lymphoma Society of America, and
as a member of National Cancer Institute Scientific Review Group D,
Subcommittee D, for Clinical Research Studies. I was also honored and
privileged to serve as a Co Chairperson of the recent Lymphoma,
Leukemia, and Myeloma Progress Review Group (LLMPRG), which was a
multidisciplinary panel of prominent scientists, clinicians, advocates,
and industry representatives convened by the National Cancer Institute
to prioritize the national research agenda for blood cancers. In the
past the blood cancers have represented a model for the treatment of
cancer with chemotherapy. Specifically, chemotherapy was pioneered 50
years ago in childhood acute lymphoblastic leukemia, and increasing the
dose and combining drugs has led to cure in the majority of cases. Use
of high doses of chemotherapy followed by bone marrow or blood stem
cell transplantation was also pioneered in blood cancers, and is
curative in some patients with leukemia. Most excitingly, the recently
approval of Glivec represents the first example of a designer drug
which specifically targets the abnormal protein that causes chronic
myelocytic leukemia. Such specifically targeted drugs represent a new
treatment paradigm with great promise for improving the outcome of
patients with cancer generally, as well as those with other illnesses
such as HIV infection. Therefore implementation of the initiatives
proposed by the recent LLMPRG will have broad and important
implications for improved medical practice.
My specific basic science and clinical interests focus on multiple
myeloma. Multiple myeloma is the second most common blood cancer,
representing 1 percent of all cancers and accounting for 2 percent of
cancer deaths. There were 14,400 new cases, 50,000 total patients
affected, and 11,200 deaths from myeloma in the United States in 2000.
Myeloma is the fourth fastest growing cancer in terms of mortality, and
importantly, is in the top 10 causes of death among African Americans.
Although traditionally considered as a disease of the elderly, the
average age of affected individuals is approximately 60 years. With the
aging of the U.S. population, its incidence is expected to further
increase. Myeloma, a bone marrow cancer like leukemia, is characterized
by the excess accumulation of antibody forming (plasma) cells in the
bone marrow, in association with the abnormal antibody (monoclonal
protein) made by these plasma cells accumulating in patients' blood
and/or urine. Affected patients develop anemia or low red blood cells
with fatigue, low white blood cells with related increased risk of
infection, and low platelet count with related risk of bleeding. The
most debilitating feature of myeloma is thinning of bone (osteoporosis)
or holes in bone (lytic lesions), with related fractures, pain, and
major limitations in quality of life and activities of normal daily
living. Other less frequent complications include kidney failure, high
blood calcium, and nerve damage. Conventional chemotherapy prolongs
survival to a median of 3 to 4 years, and high dose therapy followed by
a blood stem cell transplant can modestly extend median survival to 4
to 5 years. Tragically, few, if any, patients are cured. Treatment of
myeloma-related complications can improve quality of life for patients
and includes transfusions or growth factors to treat patients with low
red blood cell, white blood cell, or platelet counts. Importantly, the
use of bisphosphonates can slow the development of bone-related
complications, decrease related pain, and thereby improve the quality
of life of patients with myeloma.
Although conventional and high dose therapy extends survival,
disease almost always recurs and becomes resistant to all known
treatments. As a result few, if any, patients have been cured to date.
Importantly, however, major progress in our understanding of the
biology of myeloma has occurred in the past two years, providing the
framework for novel very promising therapies. The first major novel
concept is the use of drugs which not only target and kill the myeloma
cells directly, but also target their bone marrow environment to
inhibit the localization of myeloma cells in marrow, to abrogate the
production of factors in marrow which promote the growth and survival
of myeloma cells, and to block new blood vessel formation or
``angiogenesis''. Excitingly some of these new drugs also augment a
patient's own immune system to recognize and kill his own myeloma
cells, much as an infection can be cleared by our natural immune
response. Examples of these drugs include thalidomide and its
potentimmunomodulatory (IMiD) analogs, as well as proteasome
inhibitors. Even in patients whose myeloma has recurred despite all
conventional and high dose therapies, thalidomide achieves significant
responses and prolongs survival of 30 percent patients, demonstrating
that these new drugs can overcome resistance that myeloma cells have
developed to conventional therapies. Once these drugs are tested and
found to be safe and effective in patients with advanced disease, they
are rapidly evaluated as treatment for newly diagnosed patients.
Excitingly, early clinical trials suggest that treatment with these new
biologically based therapies can have an even greater impact (80
percent responses) when used as the initial therapy for myeloma. Major
laboratory research is currently ongoing to specifically identify the
targets of these new drugs in both myeioma cells and the bone marrow in
order to develop even better drugs, more selective against tumor cells,
which are both more efficacious and have fewer side effects. For
example, the revolution in our understanding of the human genome allows
for characterization of the temporal sequence of changes in expression
of up to 20,000 genes which are either upregulated or decreased in
response to drug treatment, markedly enhancing our ability to define
mechansims of drug anti-myeloma activity on the one hand, versus
mechanisms whereby tumor cells escape or resist therapy on the other.
In addition to these novel drugs targeting not only the tumor
cells, but also its interaction with the bone marrow neighborhood, two
other novel treatment approaches offer great promise. The first is
based upon basic scientific studies which can delineate those circuits
inside myeloma cells which mediate their unregulated growth, as well as
those molecular circuits which allow them to resist normal death
processes. Definition of these pathways has allowed for the development
of ``circuit breakers'', novel drugs which specifically interrupt tumor
cell growth; or ``circuit makers'', which specifically turn on death
signals inside myeloma cells. The promise of this approach is best
illustrated by Glivec, the novel drug which specifically inhibits the
abnormal protein which causes chronic myelocytic leukemia. It has
already markedly improved outcome for patients with this illness, and
has recently received FDA approval.
A third major area of promise for the treatment of blood cancers,
in particular multiple myeloma, are the immune-based therapies. These
can consist of specialized transfusions of the patient's own or a
sibling's cells which are programmed to recognize and kill patient
myeloma cells. Immune therapies also include vaccines against the
patient's tumor cell or fingerprint proteins on the tumor cell surface.
The goal here is to stimulate the patient's immune system to recognize
and reject their own tumor cells, just as natural immunity readily
clears an infection. An important advantage of these approaches is
their high selectivity and efficiency in targeting and killing tumor
cells, thereby avoiding the side effects attendant to current
conventional therapies which are non-selective and kill normal, as well
as tumor, cells.
Once novel therapies such as these are identified to be of
potential benefit to patients in laboratory preclinical studies, there
is an urgent need for rapidly moving these agents from the bench
(laboratory) to the bedside (clinic), where their clinical utility can
be assessed in treatment protocols. The need is particularly immediate
for patients with myeloma, for whom no curative therapy currently
exists. As I mentioned at the outset, a panel of prominent scientists,
clinicians, advocates, and industry representatives was convened by the
National Cancer Institute and identified research priorities in blood
cancers. Most importantly, the LLMPRG has proposed a new initiative--
The Cancer Translational Research Allied Consortium (C-TRAC). C-TRAC
represents a unique opportunity to shorten drug development time in the
United States from the current 5-10 years to 2 years through a novel
alliance among academia, industry, government, and patients, and holds
great promise to get novel targeted therapies to our patients with
blood cancers who so desperately need them.
In summary, basic science advances now offer an unprecendented
opportunity to solve the mysteries of the past and specifically and
effectively treat blood cancers. The roadmap to achieve this goal has
been laid out by the LLMPRG process of the National Cancer Institute. I
am sure that you are both personally moved and inspired by the
extraordinary courage in the face of personal adversity exemplified
here today by Geraldine Ferraro, Kathy Giusti, and the numerous other
patients here today. As a basic science and clinical researcher and
caregiver, I extend my heartfelt and genuine admiration and thanks for
your consideration and support for these research initiatives which
will markedly enhance the survival and quality of life of affected
patients worldwide.
Senator Specter. What do you think you can do within 5
years, Dr. Anderson?
Dr. Anderson. I think that within 5 years there will be
many more of the leukemias which are cured. I think that if
myeloma may not be cured, certainly it will be turned into a
chronic illness not unlike hypertension or other illnesses with
which patients can grow old gracefully, as I like to say.
Senator Specter. Thank you very much, Dr. Anderson.
I have presided at a lot of hearings. I have never heard so
much applause.
STATEMENT OF JOHN W. HOLADAY, Ph.D., CHAIRMAN AND CEO,
ENTREMED, INC.
Senator Specter. Dr. John Holaday, Chairman and CEO and Co-
founder of EntreMed, Inc., a biotech company in Rockville, MD.
He served as Chief Biochemist at the Division of
Neuropsychiatry at Walter Reed Hospital. We very much
appreciate your being here, Dr. Holaday, and look forward to
your testimony.
Dr. Holaday. It is my pleasure. I thank you, Senator
Specter, also Senator Hutchison, and my favorite Senator,
Senator Mikulski, who represents the great State of Maryland
where Rockville and certainly EntreMed are located.
It is my pleasure to tell you today that there is some good
news on the horizon. I want to share with you a story that is
part of our common passion at EntreMed and shared by many
researchers throughout the world that a new field of medicine
that has evolved around understanding the growth of new blood
vessels in various diseases like cancer might have great
promise in the treatment of multiple myeloma and various other
forms of blood cancers.
Specifically over 30 years ago, Dr. Judah Folkman, when
working at the Navy, realized that it is impossible for tumors
to grow, whether they are solid tumors or blood tumors, without
the proliferation of new blood vessels to feed that growth.
Now, in retrospect, that seems to be a rather intuitive
thought, but it has taken quite some time for that to be
recognized as a potential forefront in the field of medicine.
Subsequent to his years of effort, a young man by the name
of Dr. Robert D'Amato realized that the drug thalidomide, which
was known to cause the birth defects in the early 1960's, very
likely caused these defects by blocking the growth of blood
vessels, and thus the normal limb formation could not occur.
So, with this great step of realization, Dr. D'Amato said maybe
thalidomide is an anti-angiogenic drug that could inhibit the
growth of blood vessels and thus have efficacy in the treatment
of a variety of forms of cancer. Indeed, teaming up with Dr.
D'Amato, who first published this with Dr. Folkman in the
proceedings of the National Academy of Sciences in 1994, we at
EntreMed, along with the National Cancer Institute and Dr.
Klausner's team, proceeded rapidly toward phase II studies to
demonstrate that thalidomide has effects on a number of
different forms of cancer.
It was Dr. Folkman who actually recognized the potential of
its use in multiple myeloma who recommended to another pioneer
in this field, Dr. Barlogi, that he try thalidomide for the
treatment of that particular cancer patient. And subsequently
other leaders, such as Dr. Anderson, are continuing in this
quest to find new ways of using this old drug for a good and a
new purpose.
When we were developing this molecule, we found it was
tough to get big pharmaceutical companies, unlike us small
ones, to buy into the concept that you could resurrect a drug
with this terrible heritage. We succeeded in finding a
relationship with Celgene which was a small company like us,
but they had the opportunity to distribute thalidomide, and
through that relationship, we have been at EntreMed able to
have this drug on the market for the last 3 years, or at least
available to patients, with the leadership of such people as
Dr. Anderson and with the great hope that is provided to people
like Geraldine Ferraro. We are pleased to have had this
opportunity.
I want to also say that we are on the cusp of many new
developments in this field. It is not true that all of the
research comes from Government laboratories. We in the biotech
industry represent a very committed and dedicated group of
people whose passion it is to make a difference in the lives of
patients. In that context, we have a new series of molecules
that will come along as next generation relatives of
thalidomide, and another drug called Panzem, or 2-
methoxyestradiol, a natural substance where we have phase II
studies presently underway at the Mayo Clinic in patients with
multiple myeloma and shortly to begin with Dr. Anderson at the
Dana-Farber.
PREPARED STATEMENT
So, again, there is reason for hope. We encourage patients
as always to be very proactive in the management of their
disease and to consider, as they look forward, the
opportunities that this new field of medicine, inhibition of
angiogenesis, pioneered by Dr. Folkman so many years ago, might
have as a new way of looking at diseases and particularly
diseases of the blood.
I thank you.
[The statement follows:]
Prepared Statement of John W. Holaday
Chairman Harkin, members of the Committee, I wish to thank you for
your kindness in allowing me the opportunity to testify before the
Committee today.
My name is Dr. John Holaday. I am the founder, Chairman and CEO of
EntreMed, Inc. a biotechnology company located in Rockville, Maryland,
just outside the Beltway. I formed EntreMed in 1991 to bring
entrepreneurship to medicine. In doing so, EntreMed has assumed the
risk of revolutionizing drug discovery and development for the benefit
of patients. We now employ 120. exceptional scientists and staff, all
sharing a common passion to bring new drugs to cancer patients--
including those with solid tumors and blood cancers--in the hope of
providing them with a more livable life, and allowing them to live with
their disease, not die from it.
I would like to inform the Committee of one cancer breakthrough
that has dramatically changed thinking about how to conquer this
horrible disease and the role EntreMed plays in bringing these new
weapons to the fight against cancer. Over thirty years ago, Dr. Judah
Folkman, while working as a Naval Officer at Naval Medical Research
Institute in Bethesda, Maryland, discovered an ingenious method to
stopping tumor growth. He demonstrated that cancerous tumors require
the simultaneous growth of blood vessels to feed their malignant cells.
In doing so, he pioneered the field of medicine called
``angiogenesis.''
His quest to challenge conventional thinking in the entrenched
practice of oncology has been long and arduous, but fortunately it is
now beginning to pay off for cancer patients. Dr. Folkman's research at
Children's Hospital, an affiliate of Harvard Medical School in Boston,
has produced revolutionary molecules, such as Thalidomide, Endostatin,
Angiostatin and Panzem, that are shown to arrest cancer growth in mice
by starving tumors of their blood supply. EntreMed took these promising
molecules from the laboratory to the cancer clinic in record time, in
collaboration with Dr. Folkman, Children's Hospital and the National
Cancer Institute.
But this story goes back even further, and with the Committee's
indulgence, I will take a moment to explain it. Over twenty years ago,
Robert D'Amato was finishing high school when he won the International
Science Fair for his discovery of a new way to detect multiple
sclerosis by measuring changes in vision. His prize provided him with
the opportunity to work in my laboratories at the Walter Reed Army
Institute of Research for a summer. While there, he learned the basics
of academic medical research and went on to become one of my best
students, co-authoring twelve scientific publications with me over the
next four summers. Robert went on to earn his MD and Ph.D. degrees at
the Johns Hopkins University School of Medicine in Baltimore.
In 1992, Dr. D'Amato, now an ophthalmologist finishing his training
at the Massachusetts Eye and Ear Hospital discovered that blindness,
like cancer, depended on the growth of new blood vessels. In blindness
arising out of diabetes or age-related macular degeneration, new blood
vessels grow in the retina of the eye and block vision. In cancer, new
blood vessels sprout to feed the growth of tumors. Dr. D'Amato wondered
if there were existing drugs that could stop the growth of new blood
vessels without affecting existing ones. In this vein, he explored
whether drugs causing birth defects or changes in reproductive cycles
in women did so by blocking the growth of new blood vessels. His search
suggested the possibility that the drug thalidomide, a drug scorned for
its effects in causing deformed children in the early 1960s, might
provide the answer.
Teaming up with Dr. Folkman, the father of angiogenesis, the two
explored the idea. Soon Dr. D'Amato succeeded in convincing Dr. Folkman
that thalidomide may be an antiangiogenic drug worth further
investigation. Dr. D'Amato demonstrated thalidomide's effects in
blocking new blood vessel growth and the findings were published in the
Proceedings of the National Academy of Sciences in April 1994. Within
less than four years, our team at EntreMed, in concert with the
National Cancer Institute, took this early concept through Phase II
studies in cancer patients and obtained clinical data to authorize
orphan drug designation from the Food and Drug Administration for the
use of thalidomide in the treatment of certain forms of cancer.
We knew that it would take years for us to bring thalidomide into
routine patient use due to the notorious history of the drug and the
requirements for arduous clinical testing by the Food and Drug
Administration. As such, we sought a large pharmaceutical partnership
to help speed the process. We licensed thalidomide to Bristol Myers
Squibb, the world's largest cancer company, while continuing our
clinical trials. They decided that the challenge was too daunting, and
returned thalidomide to us after a year of study. Fortunately, we
learned that another small biotechnology company, Celgene, in Warren,
New Jersey, recently obtained orphan drug designation from the FDA for
the use of thalidomide in treating leprosy and felt they might be right
for this use as well. In December 1998, we reached an agreement between
EntreMed and Celgene that allowed thalidomide to be prescribed by
physicians on an ``off label'' use for cancer, accelerating its
availability to patients by at least three years.
After promising laboratory results at Children's Hospital and
EntreMed, pioneering clinical studies by Dr. Bart Barlogi in Arkansas
and Dr. Ken Anderson in Massachusetts, who is here today, thalidomide
has shown its benefit in treating patients with multiple myeloma.
Mr. Chairman, as the ``Angiogenesis Company,'' EntreMed is
dedicated to uncovering new treatments for cancer, including cancers of
the blood. We have shown that angiogenesis in the bone marrow plays a
major role in the progression of these ``liquid tumors,'' causing bone
erosion and progressing the disease, and antiangiogenic drugs such as
thalidomide have been shown in preclinical studies to block the
progression of myelomas and leukemias.
Today, Geraldine Ferraro is doing well as a consequence of our
collective efforts. We are proud of the role that EntreMed and our
collaborators at Children's Hospital have played in making thalidomide
available to patients with this form of blood cancer. But thalidomide
is not yet approved for use in cancer, and it has limiting side
effects. Right now in our laboratories and with collaborators at
Children's Hospital and elsewhere, we have found new and more powerful
chemical cousins of thalidomide that have fewer side effects. These
promising drug candidates are moving rapidly towards clinical trials.
Dr. D'Amato also has discovered another drug, Panzem (2-
methoxyestradiol); that in preclinical studies shows great promise in
treating multiple myeloma. It is orally available, and was shown by
EntreMed's Phase I studies in breast cancer to be without dose-limiting
toxicities. Because of EntreMed's successful efforts in demonstrating
the safety of this drug, Panzem is now in Phase II clinical trials in
multiple myeloma patients at the Mayo Clinic in Rochester, Minnesota
and further studies are to begin shortly with Dr. Anderson at the Dana
Farber Cancer Institute, in Boston.
But our passion to accelerate drug discovery and approval is not an
easy one. Industry statistics for drug development reveal a daunting
challenge. According to the Pharmaceutical Research and Manufacturer's
Association, on average only one in 5,000 potential drug discoveries
results in an approved drug twelve years later, at a cost in excess of
$400 million. Biotechnology companies are trying to discover and
develop drugs better, faster, and cheaper, and we are highly creative
in addressing unmet medical needs. Unlike big pharmaceutical companies,
however, we have limited resources.
Despite their potential to revolutionize medicine, from the
financial perspective, drug discovery and development efforts in
biotechnology are by their very nature risky, capital intensive and
protracted. The search for new drugs by biotechnology companies is like
drilling for oil or prospecting for gold. There are no guarantees, and
they are not always successful in developing products and rewarding
their shareholders that took the financial risk. We seek your
assistance in this effort. We are succeeding at providing exciting new
solutions to deadly diseases that have gone unsolved for far too long.
We need Congress' help in continuing.
Failure to nurture these new revolutionary new discoveries is like
leaving ripe apples in the orchard. Dr. Alexander Fleming is said to
have sadly lamented: ``Penicillin sat on my shelf for 12 years while I
was called a quack. I can only think of the thousands who died
needlessly because my peers would not use my discovery.'' We need to
open minds to invent new ways of attacking cancer, such as
angiogenesis. In the war on cancer, the battlefield tactic of blocking
blood vessel growth is like attacking the enemy's supply lines.
Mr. Chairman, in record time EntreMed has taken antiangiogenic
drugs like thalidomide into the clinic. Now, cancer patients receiving
EndostatinTM infusions in our Phase I human trials in the
United States and Europe are showing no adverse events while some
patients have achieved disease stabilization and tumor responses in
studies designed only to assess the safety of our drugs.
Panzem is now in Phase II studies in patients with multiple
myeloma and prostate cancer. We are making great progress in realizing
our goal of ``cancer without disease,'' where cancer patients may be
able to live full lives like diabetics, but instead of receiving
insulin, they will get antiangiogenic drugs.
Those of you with cancer or with family or friends who suffer from
the scourge of this disease know all too well the frustration and
helplessness of waiting for breakthroughs to become a reality. We hear
the cry of the dying mother, father, sister, brother, and friend. Now
we must commit the resources to win the war on cancer, and to reaffirm
our country's prominence as the world's leader in technology and
science. We can no longer afford to be patient. We must apply the
strategies and tactics of the battlefield to scientific discovery and
development in order to win this war on cancer. It is absolutely
essential that we have your help in this great battle.
With your help, Chairman Harkin and all the members of this
Committee, we cart carry on the fight with promising new cancer
strategies through the provision of greater resources to researchers
and biotechnology companies. Now is the time to invest in research that
will save the lives of our loved ones. This is a war that must be won
now!
Thank you Mr. Chairman.
Senator Specter. Thank you very much, Dr. Holaday.
We have 8 minutes remaining until blackout time at 11:30
and two Senators with rounds of 4 minutes each. Senator
Hutchison.
Senator Hutchison. Well, thank you. I will be just very
brief.
I would just like to use my time to ask you, Dr. Holaday,
to expand on the trial or study that is going on at Mayo and
what you hope to gain from that that you do not have with
thalidomide today.
Dr. Holaday. We think that the approach towards any drug
discovery process has to be multifaceted, and this particular
molecule, Panzem, also known as 2-methoxyestradiol, is a
natural substance that has shown great promise in preclinical
studies in treating various forms of multiple myeloma at the
experimental level. Based upon that promise and the fact that
it showed no dose-limiting toxicities in phase I studies in
breast cancer at Indiana University, we were encouraged to
proceed rapidly and move that into phase II studies at the Mayo
Clinic to see if what we see in the animal models is also true
in people. And we are very encouraged by what we are seeing to
date.
Senator Hutchison. Would it be more of a cure or a
treatment?
Dr. Holaday. We would like to encourage the consideration
of these new treatments as allowing people to have cancer
without disease, much as Dr. Anderson said, maybe diseases like
diabetes where you live with your insulin and you do not die
from the disease. I think that as we look modestly at our
future, we should consider that these molecules like
thalidomide, analogs of thalidomide, and Panzem are going to
offer us that opportunity.
Senator Hutchison. Well, thank you. I just once again want
to thank all of you. Every one of you on the panel has offered
something wonderful: Geraldine Ferraro for helping us start
this awareness which Senator Mikulski and I and Senator Specter
are going to try to continue; and Kathy Giusti, for your early
pioneering efforts when you did not have a whole lot of
support, but now I think you do; and Dr. Holaday and Dr.
Anderson for your commitment. We certainly look forward to
working with each of you to find a cure for each of these
diseases. Thank you.
Senator Specter. Thank you, Senator Hutchison.
Senator Mikulski.
Senator Mikulski. Thank you very much, Mr. Chairman.
Just very briefly. First of all, I am so proud of my
friend, Geraldine Ferraro, who has taken a very private matter
and taken this as usual with her wit to come forward and turn
this into a matter of public advocacy, both for research, as
well as encouraging people to be bold and courageous enough to
do the early detection. Of course, Dr. Holaday is the CEO of
one of our biotech firms in Maryland, and we had an excellent
conversation the other night.
Mr. Chairman, I am going to have maybe one question for Dr.
Holaday.
But this is a very emotional hearing for me and I think for
everybody because many of the people in this room we know
personally. I can tell you exactly where I was on a Sunday
morning when Geraldine Ferraro called me to tell me about this
disease. I literally could not believe it. I am home Sunday
morning drinking coffee. Gerry and I periodically talk on
Sundays. And she said, Barbara, I have blood cancer. It took my
breath away. So, we immediately talked about how to be
supportive.
Second, later on when she told me she was on thalidomide, I
said, Gerry, this is about birth defects. Again, I was shocked.
The reason I say all of this is that when cancer affects
someone, it affects family and it affects friends. Part of the
cure I believe is in family and friends. So, we are all in this
together. Gerry, we want you to know I think all of America,
Larry, and Ms. Giusti and all who testified, that you are part
of an American family, and we are just going to pull for you.
This is not about being a Democrat. This is not about being a
Republican. This is about being part of an American family and
really seeing what we can do to help you. So, we thank you.
And Dr. Holaday, we want to have other conversations with
you on how we can encourage biotech. Not all research is going
on at NIH. We need to have a continuum of research. We need to
have policies and tax breaks for research and development to
really have these breakthroughs.
My only concluding remark is to the doctors, to the
scientists, to the patients, may the force be with you and may
God be with the United States Senate to help you. Thank you.
Senator Specter. I thank you very much, Senator Mikulski,
and thank you all, all the witnesses, for a very extraordinary
hearing. I thank you, ladies and gentlemen, for being here and
for your enthusiasm. Now our work is cut out for us to get
increases in funding for the National Institutes of Health and
to get Federal support for stem cell research so that we can
move ahead to solve these tremendous problems.
We have received written statements that we will include in
the record.
[The statements follows:]
Prepared Statement of Beverly S. Mitchell, M.D., President, American
Society of Hematology
Senator Harkin and members of the Subcommittee, thank you for
holding this very important hearing today on the hematologic
malignancies. My name is Beverly Mitchell and I'm Chief of the Division
of Hematology and Oncology and Associate Director of the Lineberger
Comprehensive Cancer Center at the University of North Carolina at
Chapel Hill. I am President of the American Society of Hematology
(ASH), which has over 10,000 scientists and clinicians united by their
common interest and commitment to understanding and curing blood
disorders. The Society thanks the Subcommittee for their unwavering
support of biomedical research and fully supports the Ad Hoc Group for
Medical Research Funding recommendation of an appropriation of $23.7
billion for the National Institutes of Health in fiscal year 2002.
ASH is proud that NIH-sponsored research in hematology has led to
important discoveries with broad applicability to treating heart
disease, strokes, end-stage renal disease, cancer and AIDS, among other
human diseases. For this reason, the Society is firmly committed to
broad-based support for biomedical research and to the existing peer-
review process as the best way to identify and prioritize scientific
grants. Since the study of blood and its disorders involves a number of
areas, hematologists receive funding from multiple NIH Institutes. The
Society would like to particularly commend the leadership of the NHLBI,
NIDDK, and NCI for their vision and superb stewardship.
I would specifically like to congratulate Dr. Richard Klausner and
his colleagues at the NCI as well as the many scientists, clinicians,
and advocates that worked on the Leukemia, Lymphoma, and Myeloma
Progress Review Group, also known as the blood cancers PRG.
Historically, research in the blood cancers supported by NCI has
provided the biological framework for new directions and progress in
the research and treatment of all cancers. Now, the convergence of new
tools and technologies presents us with the opportunity to place
discovery and development of cancer prevention and treatment
interventions on a firm scientific footing. There is a sense of
excitement in the hematology community particularly with the rapid
evolution of molecular biology that has already led to a number of
major discoveries. The Lymphochip, for instance, is a DNA microarray
that gives us an unprecedented view of the molecular machinery of blood
cancer and will be used to study samples of thousands of patients with
all varieties of lymphoma and leukemia. You have also heard of Gleevec,
or the leukemia pill, which offers effective new treatment for chronic
myelogenous leukemia or CML.
It is on the heels of these and of other important discoveries that
the NCI's blood cancers PRG completed its excellent review of the basic
science and clinical challenges to advancing our understanding of the
blood cancers. The report is incredibly comprehensive, covering not
only issues in basic biology and clinical trials methodology, but also
epidemiology, collaboration, education, communication, and behavioral
and outcomes research. Immediate priorities identified in the report
include increased understanding of the basic biology and the key
environmental factors that lead to blood cancer, increased
translational research resources, identifying populations at high risk,
and improving access to quality care through accurate and timely
distribution of information and increased training of physicians. The
centerpiece of the report is the development of a Cancer Translational
Research Allied Consortium to bring together academia, industry,
government, and patients to shorten drug development time for the
hematologic cancers from between 5 and 10 years to 2 years.
The American Society of Hematology strongly urges that a budget and
business plan be developed to guide implementation of the blood cancers
PRG report recommendations. ASH is concerned that without such a plan,
specific steps for collaborative action to accelerate the development
of new therapies for blood-related cancers will go unidentified.
A budget and business plan would help us increase our understanding
of myelodysplasia, for example. Myelodysplasia is a serious disorder
that occurs in older patients and in individuals who have undergone
previous radiation or chemotherapy treatment for cancer and/or blood
diseases such as aplastic anemia. Standard treatment is currently
limited to blood product transfusions, and, in some cases, chemotherapy
treatments if the disease develops into acute leukemia. There is no
curative treatment other than bone marrow transplantation, which is
effective in only a small percentage of patients. Among the victims of
myelodysplasia are the astronomer and great promoter of science, Carl
Sagan. Also, at the end of his life, your former colleague, the
honorable Senator Paul Tsongas, battled myelodysplasia that developed
as a result of the treatment that he received for his lymphoma. As the
lifespan of the average American increases, myelodysplasia, a formerly
rare disorder, is becoming more common. A budget and a blueprint for
the PRG will lead to recognition and support for research that will
help us find ways to further unravel the mystery of myelodysplasia so
that we are able in turn to extend the lives of patients, many of them
already survivors of cancer and other devastating diseases.
In addition to urging you to support these important follow-up
activities to the tremendous PRG effort, I would also like to take this
opportunity to highlight an important legislative effort in the
reimbursement arena that complements the scientific progress in
treating blood cancer. I would like to bring to your attention the
Access to Cancer Therapies Act of 2001, introduced by Senator Olympia
Snowe and Representative Deborah Pryce. If enacted, the legislation
would update Medicare's reimbursement policy to cover all oral anti-
cancer drugs since Medicare currently only pays for an oral cancer drug
if it has an equivalent that can be administered intravenously,
incident to a physician's service in a doctor's office or in a hospital
outpatient department.
The American Society of Hematology strongly urges you and your
colleagues to sign-on as a co-sponsor of the Access to Cancer Therapies
Act to help ensure its passage in this session of Congress.
The Access to Cancer Therapies Act is critical in particular
because new oral anti-cancer drugs are emerging as an indispensable
feature of quality cancer care and will replace or make more effective
current therapies largely based on intravenous administration. Today,
these and other oral cancer treatments are only 5 percent of the
market, but are expected to increase to 25 percent or more by the end
of this decade. Furthermore, without Medicare coverage, most of these
oral drugs will require out-of-pocket payment and access for cancer
patients will be unfairly influenced by the patient's ability to afford
these new approaches to treatment. For many cancer patients, especially
those in rural areas, oral drugs are not only preferred, but are
absolutely necessary as life-extending treatment.
In conclusion, this is an exciting time to be engaged in biomedical
research and we are proud that ASH members are participating in so many
innovative studies. ASH applauds the excellent stewardship of the
hematology research portfolio, particularly at the NCI. The
opportunities in hematologic malignancy research are immense. I believe
that with a budget and a blueprint for implementing the recommendations
of the PRG, the effort will stimulate the necessary partnerships and
cooperative ventures involving multiple academic centers for clinical
research projects to succeed in bringing improved therapies for
patients. At the same time, we must make sure that mechanisms for
reimbursement, such as that provided by the Access to Cancer Therapies
Act, are in place so that patients can receive the very best in cancer
treatment.
ASH sincerely hopes that you will be able to continue your
longstanding policy of support for cancer research and access to
quality cancer care.
______
Prepared Statement of Howard B. Urnovitz, Ph.D., Scientific Director,
Chronic Illness Research Foundation and Chief Science Officer, Chronix
Biomedical
Mr. Chairman, I am grateful to the Committee for allowing me the
opportunity to submit written testimony in support of this hearing
being held to examine issues regarding blood cancers such as leukemia,
lymphoma, and myeloma. After receiving my doctorate degree in
Microbiology and Immunology from the University of Michigan in 1979, I
did a postdoctoral fellowship at Washington University School of
Medicine, St. Louis, studying research models for multiple myeloma.
Currently, I am Scientific Director of the Chronic Illness Research
Foundation and Chief Science Officer of Chronix Biomedical, a privately
owned company conducting research focused on identifying predictive,
diagnostic and therapeutic genomic markers and targets in chronic
diseases.
I am providing this testimony to emphasize the importance of
providing effective laboratory markers in clinical trials of new
multiple myeloma therapeutic management strategies. The correct
selection of laboratory markers can ensure the most effective
treatment, thereby maximizing drug efficacy and minimizing adverse
effects.
Multiple myeloma is like most chronic illnesses with respect to its
unknown origins and progressive mechanisms. This disease can remain
asymptomatic or smoldering for many years. In the symptomatic phase the
most common complaints are bone pain and fatigue. Treatment improves
the clinical situation in only about 60 percent of the patients.
Multiple periods of remission and relapse can occur. Currently the
disease is incurable.
In December 2000, Dr. Brian G. M. Durie and I reported on the
discovery of a new surrogate marker for Multiple Myeloma (``RT-PCR
Amplicons in the Plasma of Multiple Myeloma Patients Clinical Relevance
and Molecular Pathology,'' Acta Oncologica Vol. 39, No. 7, pp. 789-
796). Dr. Durie has written over 250 myeloma research papers, as well
as numerous book chapters. He is Chairman of the Board and Scientific
Advisor to the International Myeloma Foundation (www.myeloma.org),
which he co-founded with Brian and Susie Novis. Dr. Durie is a
Professor of Medicine and on staff at Cedars Sinai Comprehensive Cancer
Center, Division of Hematology--Oncology, Cedars Sinai Medical Center,
Los Angeles, CA.
Our publication, which is submitted along with this testimony,
describes the surprising discovery of genetic material, RNA, in the
plasma (i.e., the cell-free portion of the blood) of multiple myeloma
patients. RNA is part of the genetic machinery of our bodies and is
rarely detected outside of cells. We identified the RNA as being part
of the recently mapped human genome. The most important observation of
this study was that the detection of a specific RNA marker seemed to
correlate with the clinical status of the patient, that is, to relapse
or remission. In patients who were in remission in response to
successful treatment, the RNA marker became undetectable; in those
patients in whom treatment was unsuccessful, the RNA marker continued
to be detected in their plasma.
Since the publication of this study, we have applied these new
methods derived from the information catalogued by the Human Genome
Project to identify many more RNA markers in other chronic diseases.
With support from Dr. Durie and the International Myeloma Foundation,
our preliminary data suggest that plasma RNA expression profiles will
be strong candidates for monitoring the success or failure of drug
therapies. My colleagues and I feel that the introduction of new
concepts in identifying surrogate markers will have a strong impact on
our fight against cancer.
I want to thank the Committee for its attention in addressing the
need to provide early detection and more effective treatments in the
battle being waged against debilitating chronic diseases, particularly
multiple myeloma.
______
Prepared Statement of Mrs. Rafael Mora
I am submitting testimony on behalf of my spouse who went home to
the Lord on April 26, 2001 who had multiple myeloma cancer. My spouse
began to have back pain in the beginning of the year 2000, and we
sought medical attention immediately through our HMO. Numerous delayed
appointments took place, followed by mis-diagnosis such as back injury,
muscle spasm, skeletal, disc, hernia, sciatic nerve, etc. Finally some
tests, and labs were done and not until June 2000 was the cancer
diagnosed at the Washington Cancer Institute, where our HMO had finally
referred us to after wasting so much precious time.
We began radiation immediately followed by chemotherapy. The goal
was for my spouse to receive a bone marrow transplant which would take
place at John Hopkins Hospital in November 2000. My spouses care was
coordinated through our HMO and Johns Hopkins Hospital. Just before the
transplant was to take place we were informed by John Hopkins that lab
results done 3 weeks earlier by our HMO--had only now been received
from our HMO--and it showed ``enzymes'' rising in my spouses liver and
we would need to postpone the bone marrow transplant and begin
chemotherapy immediately. John Hopkins said that we needed to monitor
my spouses liver, because if his liver was not ``normal'' it would be
fatal to move forward with the bone marrow transplant. On January 7--
the 4th cycle of chemotherapy ended and my spouse was scheduled for a
liver biopsy which did not take place till January 18 because he became
ill with a bad cold. On Feb. 8 we received via e-mail from John
Hopkins--a message that it would be fatal to move forward with the bone
marrow transplant because his liver was not normal for a transplant
after reviewing tests and conferring with other liver/pathologist
specialist. I and my spouse believed the chemotherapy caused the damage
to liver.
By this time we were unable to participate in any clinical studies
due to my spouses stage of disease and John Hopkins recommended
thalidomide treatment as the next course in treatment and our HMO
agreed. However, the thalidomide treatment did not begin till 2 months
after the chemotherapy had ended because the HMO doctor was out of town
and no one else could write the prescription for thalidomide, although
now--they say otherwise.
Amazingly with all the cruel delays, the treatment of thalidomide
showed very hopeful results. However, my spouse began taking new pain
medicines on April 10 and became violently ill on April 19. We sought
medical attention with our HMO and was told ``it was the myeloma and
that we needed to manage the pain''. We did not agree and we did not
take anymore of the pain medicines. My spouse continued to eat and
drink fluids and have bowel movement but one day later he awoke
disoriented and we went to the hospital emergency. The 3 doctors on
duty informed us that his kidneys had shut down and they were trying to
save him. Those physicians at the hospital felt that most likely the
pain medicines my spouse received, had caused his kidneys to shut
down--we would not know for certain till a biopsy of the kidneys were
done. For the first 3 days in the hospital my spouse continued to eat
and have bowel movement and although it looked like his kidneys were
recovering, dialysis was ordered by the two attending physicians. One
physician stated ``you will die without dialysis''. On April 25 a port
was placed on the right side of my spouses upper chest in the vein that
runs from the neck area. It was not properly placed and my husband
hemorrhaged for 12 hours. We were also told that the injection of
heparin he received during his dialysis caused the bleeding which they
continued to refer to as ``an ooze''. My husband went into shock at
1:30 a.m. and held on till 8:15 p.m. the next evening when he went home
to the Lord on April 26, 2001.
Our son never had the opportunity to have that crucial important
time with his father before he went home to the Lord. My spouse
suffered in the hospital due to the severe inadequate care. His
diagnosis was well late into the disease because of the seriously
inadequate health plan services we received from our HMO--constant
delays of appointments, testing and lab services.
All of this should not have happened. It has been a terrible,
terrible, painful and hurtful experience. My spouse was 60 years old,
he was a very active and fit person all his life and even after the
disease struck him he continued to do all that he could to help beat
this cancer. Our 13 year old son is still in trauma and when he grieves
for his father he gets a nose bleed. He is afraid to cry because of the
nose bleed. Our family has been devastated.
The HMO health service and the Hospital health service received is
shameful and will never be forgotten. This has been a nightmare. I hope
this hearing will bring to light how many people have suffered, and
their families because of health insurance providers, doctors and staff
that are not specialized to handle cancer cases, who however, continue
to treat patients and write prescriptions as if every person were just
a number.
So what do I hope this testimony will accomplish? I hope and pray
that no more people will have to suffer due to wasted precious time by
going to their physician, HMO or health insurance provider. I urge
everyone to get into a cancer center immediately if there is any hint
that you may have something cancerous or unexplainable. These cancer
centers specialize and have the great experience needed in the battle
against cancer, and yes it is a battle. These cancer centers will do
all that they can for you. They will not let you suffer and lie to you.
They will not give you pain medicines without warning you that your
kidneys could give out--they know exactly what you should receive and
what you should not. And if any problems arise they will have exact
history and be able to treat you immediately without guessing or
suggesting it is your disease. These cancer centers have very serious,
well educated doctors, researchers and staff who desperately are trying
to find cures to help people. They have controlled environments and
understand and know what patients need and they are comforting. I
firmly believe that what my spouse and many, many others have to go
through would not happen at these cancer centers. You may ask how do I
know these things. Well, althrough my spouses battle we continued to
educate ourselves and looked into any study we could find and read up
on numerous cancer centers in this country from the west to the east
coast, and other countries as well and what they are doing. Our desk at
home is a huge pile of cancer studies, research and information.
I must mention that by having my spouse go through all those
meaningless appointments in the beginning with the HMO and holding out
to refer him to a cancer center just to save a few pennies was the
worse situation ever encountered. That is why our health care system is
so burdened because instead of getting to the root of problems,
precious time is being wasted and money, by making clients go through a
song and dance with their very own lives.
My spouse, our sons father--can never be replaced. It is a sorrow
that will live with us. More funding is crucial for cancer centers
around the nation and world providing specialized treatment in cancer.
In closing, according to NBC news release on May 11, 2001, over 98,000
deaths occur each year due to prescription medicines (the pain medicine
oxycotin was the feature story). We are still waiting for the full
autopsy report from the hospital.
Let us not waste precious time--IT IS A RACE FOR THE CURE.
CONCLUSION OF HEARING
Senator Specter. Thank you all very much for being here,
that concludes our hearing. The subcommittee will stand in
recess subject to the call of the Chair.
[Whereupon, at 11:28 a.m., Thursday, June 21, the hearing
was concluded, and the subcommittee was recessed, to reconvene
subject to the call of the Chair.]