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Emerging
Therapies
for Multiple
Myeloma
Patient Brochure
NeoRx Corporation
300 Elliott Avenue West, Suite 500
Seattle, Washington 98119-4119
www.neorx.com
© 2004 NeoRx Corporation
All rights reserved.
NRX-100-2500
October 2004
Printed in USA

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Multiple Myeloma
Multiple myeloma is a treatable, but incurable
disease. At present, there are approximately
50,000 people in the United States living with
multiple myeloma. Approximately 15,300 people
are diagnosed with multiple myeloma each year.
Multiple myeloma (also known as myeloma or
plasma cell myeloma) is a cancer that affects a
specific type of white blood cell called the plasma
cell. Plasma cells, which are a type of B-lymphocyte,
are part of the body's immune system. Plasma
cells begin their development in the bone marrow,
and produce antibodies or immunoglobulins that
move through the bloodstream to help fight
infection and disease. In multiple myeloma, the
body produces an excessive number of abnormal
or malignant plasma cells called myeloma cells.
Myeloma cells collect in the bone marrow and in
the area of hard bone that supports the bone
marrow, causing holes and even fractures to
develop in any area of the skeleton. It is common
for myeloma cells to collect in many bones, forming
many tumors and causing multiple problems.
This type of myeloma also involves circulation of
myeloma cells in the body and the presence of
M protein in the urine. This more common form of
the disease is referred to as secretory multiple
myeloma. Another form of myeloma is a
plasmacytoma, which forms when myeloma cells
collect in only one bone and create a single
tumor. A plasmacytoma may eventually turn into
secretory myeloma.
Although multiple myeloma affects the bones, it is
a hematologic or blood-borne disease that
originates in the bone marrow. Bone disease in
myeloma is very different from primary bone
cancers like osteosarcoma or Ewing's sarcoma,
which begin in the hard outer part of the bone, or
tumors originating in one area of the body such
as breast, prostate or lung cancer that spread
(metastasize) to the bone.
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The excessive number of myeloma cells and
Response to therapy may fall into one of several
the amount of abnormal antibodies that they
categories. The amount of M protein in the urine
produce (also known as monoclonal or M protein)
or blood serves as a measure of the response to
observed in multiple myeloma can cause serious
treatment.
medical problems. Myeloma cells produce or
stimulate the production of cytokines (chemical
Response Category
Description
messengers in the blood) that damage and
weaken bones, causing bone fractures and often
Responsive Disease
Decrease in M protein of at
severe pain. When bones are damaged, calcium
least 50%
is released into the blood. Excessive levels of
calcium (hypercalcemia) can lead to loss of appetite,
Plateau
Response that has reached
nausea, thirst, fatigue, weakness, restlessness and
a certain point and does
confusion. Myeloma cells in the bone marrow may
not change
also prevent the development of normal plasma
Stable Disease
Decrease in M protein that
cells and other important blood cells. Patients
with myeloma are, therefore, more susceptible to
has not reached 50%, but
infection, anemia, and bleeding because of
remains stable during
lowered platelet counts. Myeloma patients may
therapy or after therapy is
also have kidney problems because excessive
stopped
calcium and M protein prevent the kidneys from
Progressive Disease
Myeloma continues to
filtering and cleaning the blood properly.
worsen despite therapy
The diagnosis and treatment of myeloma is a
Relapsed Disease
Myeloma initially responded
complex process. No single test result determines
to treatment, but has begun
the treatment or prognosis of myeloma.
to progress again
Management of myeloma is tailored to the individual
patient based on many factors including:
Refractory Disease
Myeloma that has not
responded to therapy or
· Results of a physical exam
relapsed disease that does
· Results of laboratory tests
not respond to subsequent
· The stage or classification of disease
treatment
· Age and general health
Primary Refractory
Myeloma that does not
· Symptoms
Disease
respond to initial or
subsequent therapy
· Presence of complications of the disease
· Previous treatment for the disease
Cures have not been documented in patients with
myeloma. The best outcomes achieved have
been molecular complete responses (no evidence
of myeloma cells in the bone marrow using
the most sensitive laboratory molecular testing
techniques available). The definition of a
molecular complete response is constantly
evolving as technology improves and more
sensitive techniques are developed.
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New Therapies for
the Treatment of Myeloma
Treatment options for patients with refractory
myeloma include participation in a clinical trial of
new agents which may involve bone marrow
or stem cell transplant. According to the
Multiple Myeloma Research Foundation
(www.multiplemyeloma.org) and the International
Myeloma Foundation (www.myeloma.org), a
number of new agents and therapies are available
or are in the later stages of clinical development
for the treatment of myeloma.
Skeletal Targeted Radiotherapy
Skeletal Targeted Radiotherapy (also known as
STRTM, 166Ho-DOTMP; NeoRx® Corporation) is a
bone-seeking radioactive drug that is being
Skeletal Targeted Radiotherapy (STRTM, 166Ho-DOTMP)
developed for use with high-dose chemotherapy
and stem cell transplantation for the treatment of
In early clinical trials of STRTM, many patients
myeloma. STRTM consists of two components
experienced bladder problems and a few also
which are bound together and administered
experienced kidney problems. Bladder problems
intravenously as a single agent. The first component,
are preventable using a technique called
DOTMP, attaches to bone. The second, 166Ho, is
continuous bladder irrigation (CBI). Kidney problems
radioactive holmium, which has the ability to
predominantly occurred in patients who received
destroy cancer cells. In an effort to provide more
the highest doses of STRTM which are no longer
direct penetration of the therapeutic radiation,
used. A small number of these patients died of
STRTM targets radiation to the bone, thereby
kidney failure. In all current and future STRTM trials
potentially reducing the exposure of normal
patients will undergo CBI and receive intravenous
organs and tissues to damaging radiation.
(IV) fluids to assist in clearing excess radiation
from the kidneys and bladder.
STRTM is designed to be used in combination with
STRTM is followed by high-dose chemotherapy
high-dose chemotherapy producing a direct
with the drug melphalan. The administration of
therapeutic effect on the tumor sites in the bone
chemotherapy at doses higher than those used in
plus a general bone-marrow effect to destroy
conventional regimens is often used to treat
myeloma cells in the bone marrow. Patients
myeloma. While these higher doses are more
receiving STRTM and high-dose chemotherapy with
effective in killing myeloma cells, they also destroy
melphalan will require stem cell transplantation to
the normal blood-forming cells in the bone marrow.
restore their bone marrow to its normal functioning.
Because a person cannot survive without these
blood-forming cells, high-dose chemotherapy is
administered followed by stem cell transplantation
with cells harvested from the patient (autologous
transplant) or from a donor (allogeneic transplant).
Comprising <1% of all cells in the bone marrow
and even fewer in the peripheral blood, stem cells
can divide and develop into any one of the three
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main types of cells found in the blood: red blood
Other New Agents
cells; white blood cells; or platelets.
Two new agents, thalidomidea and bortezomibb,
target unique biochemical pathways. Thalidomide
Prior to high-dose chemotherapy, the first step
is an oral immunomodulatory agent currently
in the process of stem cell transplantation is the
approved for the treatment of leprosy. It is being
collection of stem cells from the patient (autologous
studied alone and in combination with other drugs
transplant) or donor (allogeneic transplant). Cells
for the treatment of myeloma. Thalidomide may
may be collected from the bone marrow or from
have multiple areas of activity in the treatment of
the peripheral blood. Stem cells may be frozen
myeloma. It may: 1) inhibit the growth of new
and stored until the patient needs them.
blood vessels (angiogenesis); 2) alter the adhesion
Following high-dose chemotherapy the stem cells
of cells to the bone marrow supporting cells; and
are infused back into the patient. These stem
3) stimulate the immune system to attack tumor
cells travel to the bone marrow where they begin
cells. Common side effects of thalidomide include
to produce new blood cells, replacing those lost
drowsiness/somnolence, peripheral neuropathy,
during high-dose chemotherapy.
dizziness/orthostatic hypotension, and neutropenia.
Two other immunomodulatory drugs similar to
Most of the potential side effects of transplanta-
thalidomide, RevlimidTM (formerly RevimidTM,
tion are the result of high-dose chemotherapy.
lenalidomide, CC-5013) and ActimidTM (also
The more common temporary side effects include
known as CC-4047) are also under development
nausea, vomiting, fatigue, diarrhea, mouth sores,
for the treatment of myeloma. Bortezomib is the
and hair loss. Because high-dose chemotherapy
first of a new class of medicines called proteasome
destroys the blood-producing cells in the bone
inhibitors. It is approved by the U.S. Food and
marrow, patients are susceptible to infection,
Drug Administration (FDA) for the treatment of
anemia, and bleeding until engraftment of the new
myeloma patients who have received at least two
stem cells has occurred. Stem cell transplantation
prior therapies and have demonstrated disease
is not appropriate therapy for everyone due to the
progression during the last therapy. Common
toxicities and risks involved. Patients over the age
side effects of bortezomib includes nausea,
of 65-70 years, or those with a poor performance
fatigue, decreased blood counts, and peripheral
status or even minimally impaired kidney function
neuropathy. Administered intravenously,
may not be eligible for this type of therapy within a
bortezomib reversibly blocks proteasome (a key
clinical trial.
enzyme complex found in all cells that helps
regulate cell growth). By inhibiting proteasome,
STRTM as a treatment for cancers involving the
bortezomib promotes apoptosis (programmed
bone is being tested in other forms of cancer
cell death). Bortezomib is also currently being
where stem cell transplantation is used in support
studied in combination with other drugs for the
of high-dose radiation followed by high-dose
treatment of myeloma.
chemotherapy. Such diseases may include
leukemias, metastatic bone disease due to breast,
While myeloma remains a serious disease with an
prostate or lung cancers, and for primary bone
unmet therapeutic need, the outlook for improved
cancers such as Ewing's sarcoma.
treatment with increased rates of response,
prolonged survival and improved quality of life is
encouraging. New therapies under development
target the bone and biochemical abnormalities
unique to myeloma cells. As many new treatment
regimens remain investigational, patients and their
families should strongly consider participation in
clinical trials.
aThalomid®; Celgene Corporation bVelcade®; Millennium Pharmaceuticals, Inc.
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Glossary
that may build up in the bladder following certain
types of radiation therapy or chemotherapy
Allogeneic stem cell transplant: Transplant in
which bone marrow or peripheral blood is taken
Cytokine: Soluble chemical produced by cells
from a donor and infused ("donated") to a patient
that has an effect on other cells
who has received high-dose chemotherapy or
radiation therapy
Hematologic: Pertaining to the blood
Anemia: Decrease in the number of oxygen-carrying
High-dose chemotherapy: Administration of
red blood cells in the blood; associated with
higher, more effective doses of chemotherapy;
tiredness and weakness
because high-dose chemotherapy destroys the
bone marrow, a stem cell transplant is required to
Antibody: Protein produced by plasma cells
replenish blood-forming bone marrow cells
that is generated in response to a foreign body
(antigen); an antibody is also known as an
Hypercalcemia: Condition characterized by
immunoglobulin
elevated levels of calcium in the blood due to
increased bone destruction
Apoptosis: Natural cell death which occurs in
the life cycle of nearly all cells; in cancerous cells
Immune Response: A bodily defense reaction to
the signals for cell death are blocked or altered
invasion by a foreign body or pathogen such as a
and natural cell death does not occur resulting in
virus, bacteria or tumor cell; the immune system
overgrowth and longer life of the malignant cell
produces antibodies in an attempt to destroy or
fight the foreign invader
Autologous stem cell transplant: Transplant in
which bone marrow is taken from the patient,
Immunoglobulins: Produced by plasma cells,
stored and frozen to be infused following high-dose
antibodies generate a response to a foreign
chemotherapy and/or radiation therapy
protein (antigen), thus producing an immunity
against that protein
Bone marrow: Soft, spongy tissue found in the
center of many bones; area where red blood cells,
Lymphatic system: A system of soft tissues and
white blood cells and platelets are produced;
vessels similar to blood vessels located
plasma cells arise from the bone marrow
throughout the body which contain and circulate
lymphocytes, a specific type of white blood cell
B-lymphocyte: A specific type of white blood cell
that defends the body against toxins and
that is found in the blood and lymph nodes that
pathogens such as bacteria or viruses
participates in the body's immune response
Melphalan: (also known as Alkeran®) Type of
Complete response: Multiple myeloma treatment
chemotherapy often used in the treatment of
outcome where there is no detectable M protein in
myeloma; belongs to a class of drugs called alkylating
the serum and urine (using an immunofixation assay)
agents; at standard doses does not require stem
and a normal percentage of plasma cells in the
cell transplantation; melphalan is typically given as
bone marrow or absence of myeloma cells in the
an oral drug; in the transplantation setting,
bone marrow by standard staining techniques
melphalan is administered intravenously
Continuous bladder irrigation (CBI): A procedure
Metastasis: Process by which tumor cells travel
where a catheter is inserted into the bladder
from the initial or primary site (e.g., breast, prostate,
allowing for continuous flushing of the bladder
lung) to other parts of the body (e.g., bone, liver,
with fluid; CBI allows for rapid clearance of toxins
lung, brain) and develop into tumors; metastases
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can also occur when tumor cells spread from the
activity is blocked, tumor cells may undergo
initial site to nearby, adjacent tissues
apoptosis as a mechanism of the drug's action
Molecular complete response: No evidence of
Proteasome inhibitor: A new class of medicines
myeloma cells in the bone marrow using sensitive
that reversibly blocks proteasome and promotes
molecular techniques in laboratory testing
apoptosis in cancer cells
Monoclonal (M) protein: Identical immunoglobulin
Primary refractory myeloma: Myeloma that does
(antibody) protein produced by myeloma cells;
not respond to initial or subsequent therapy
M protein is found in the blood or urine and
is used as a marker for the amount of myeloma
Refractory myeloma: Myeloma that has not
disease present in the body
responded to initial therapy, as well as relapsed
myeloma that does not respond to subsequent
Multiple myeloma: An uncommon blood-borne
treatment
cancer which originates in the bone marrow and is
associated with the excessive production of
Secretory myeloma: The more common form of
abnormal or malignant plasma cells (myeloma cells)
multiple myeloma that typically involves disease
in the bone and bone marrow, circulation of
Myeloma cell: A plasma cell that has become
myeloma cells in the body, and the presence of
cancerous or malignant; the abnormal cell
M protein in the urine
responsible for multiple myeloma; excessive
numbers of identical myeloma cells producing an
Stem cells: Parent cells that grow and divide to
overabundance of immunoglobulins (M protein)
produce red blood cells, white blood cells, and
are responsible for symptoms characteristic of
platelets; found primarily in the bone marrow but
multiple myeloma
also found in the peripheral blood or venous system
Peripheral neuropathy: Abnormal or decreased
Skeletal Targeted Radiotherapy: (also known as
sensation or burning/tingling in the hands and
STRTM, or 166Ho-DOTMP) An investigational
feet; peripheral neuropathy may or may not
bone-seeking radioactive drug under development
resolve following the end of chemotherapy for
with high-dose chemotherapy and stem cell
myeloma
transplantation for the treatment of myeloma;
STRTM consists of two components: DOTMP
Plasma cell: Antibody-secreting immune cell that
which targets and attaches to bone and
develops from a B-cell
radioactive holmium, 166Ho, which can destroy
cancer cells; the goal of STRTM is to target
Plasmacytoma: Single tumor comprised of
radiation to the bone and bone marrow; by
malignant plasma cells that occurs in bone or soft
attempting to target therapeutic radiation to the
tissue; some patients may also develop secretory
bone, STR may reduce radiation exposure to
myeloma
other normal organs and tissues
Proteasome: A complex of enzymes found within
TTP/HUS: Thrombocytopenic thrombotic
cells that play a key role in the regulation of cell
purpura/hemolytic uremia syndrome is a rare
function and growth; proteasomes break down
syndrome associated with radiation damage to
and clear out proteins after they have done their
the kidneys; findings include abnormal blood
job and are no longer needed; some cancer cells
clotting in small vessels, low platelet counts
appear to be particularly dependent on
leading to bleeding, and kidney failure which may
proteasomes to grow, survive and undergo
require dialysis and can result in death
programmed cell death (apoptosis); if proteasome
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Venous system: Part of the circulatory system
which carries blood throughout the body; the
venous system consist of veins which carry blood
away from muscles and organs and back to the
heart and lungs
Patient Resources for Myeloma
1. American Cancer Society®
www.cancer.org
All About Multiple Myeloma
2. International Myeloma Foundation
www.myeloma.org
3. Multiple Myeloma Research Foundation
www.multiplemyeloma.org
4. National Cancer Institute®
www.cancer.gov
Cancer Information Service 1-800-4-CANCER
What You Need to Know AboutTM Multiple Myeloma
Taking Part in Clinical Trials: What Cancer
Patients Need to Know
5. The Leukemia and Lymphoma Society®
www.leukemia-lymphoma.org
Patient Services: Multiple Myeloma
#1, #4, #5 are registered trademarks of their
respective organizations.
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