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Powerful thinking advances the cure

Powerful thinking advances the cure

About the Multiple Myeloma

supporting a pipeline of more than

Research Foundation

50 promising compounds and combina-

The Multiple Myeloma

tion treatments, including more than

Research Foundation

40 clinical trials we advanced through our

(MMRF) was founded

sister organization, the Multiple Myeloma

in 1998 by identical

Research Consortium (MMRC).

twin sisters Kathy Giusti

and Karen Andrews soon after Kathy was

As the multiple myeloma communitys

diagnosed with multiple myeloma, an

most trusted source for information, the

incurable blood cancer. The mission of the

MMRF supports patients from the point

MMRF is to relentlessly pursue innovative

of diagnosis throughout the course of

means that accelerate the development of

the disease. No matter where you are

next-generation multiple myeloma treat-

in your journey with multiple myeloma,

ments to extend the lives of patients and

you can count on the MMRF to get you

lead to a cure.

the information you need about multiple

myeloma and its treatment options,

Thanks to the support and generosity

including clinical trials. All information

of people like you, and by working

on our Web site,, is

closely with researchers, clinicians and

tailored to patients by disease stage so

our partners in the biotech and pharma-

we can make sure you get information

ceutical industry, we helped bring multiple

you need at the right time.

myeloma patients five new treatments

that are extending lives around the globe.

To learn more about the MMRF, visit

Today, we are on the cusp of the next

breakthrough treatment, and are

Accredited by:

2012, Multiple Myeloma Research Foundation

Introduction 2
What Is Multiple Myeloma?

How Common Is Myeloma?

What Causes Myeloma?

How Does Myeloma Affect the Body?

What Are the Symptoms of Myeloma?

What Tests Are Done to Diagnose Myeloma?

Seeing a Myeloma Specialist

How Is Myeloma Classified and Staged?


Can Outcome Be Predicted?


What Are the Possible Goals of Treatment?


How Do You Decide Which Treatment

Is Appropriate?


How Do You Know if a Treatment Is Working?


What Therapies Are Used in Myeloma?


Initial Therapy for Newly Diagnosed

Symptomatic Disease


Treatment Options for Relapsed or

Refractory Myeloma


What Does the Future Look Like for

Myeloma Treatments?


Questions to Ask Your Doctor




This booklet is designed primarily to
help individuals with newly diagnosed
multiple myeloma and their friends and
families better understand this disease.
The booklet explains what myeloma is
and how it develops within the body.
Words that may be unfamiliar are bolded
throughout the text at first mention and
defined in the Glossary (page 25). Learning as much as possible about multiple
myeloma will help you be more involved

The MMRF booklet,

Multiple Myeloma:
Treatment Overview,
and the MMRF Web site
( provide more information
about current therapies
for myeloma and emerging treatment options.

in making decisions about treatment.

The information in this booklet is not
intended to replace the services of trained

What Is Multiple Myeloma?

healthcare professionals (or to be a

Multiple myeloma is a blood cancer that

substitute for medical advice). Please

develops in the bone marrow (Figure 1).

consult with your healthcare professional

In myeloma, normal antibody-producing

regarding specific questions relating to

plasma cells transform into malignant

your health, especially questions about

myeloma cells. Myeloma cells produce

diagnosis or treatment.

large quantities of one antibody (or immunoglobulin) called monoclonal (M) protein. These malignant cells also crowd out
and inhibit the production of normal blood
cells and antibodies in the bone marrow.
In addition, groups of myeloma cells cause
other cells in the bone marrow to remove
the solid part of the bone and cause
osteolytic lesions, or soft spots in the
bone (Figure 2). Although common, these
lesions or other signs of bone loss do not
occur in all individuals with myeloma.

2 | Multiple Myeloma Disease Overview

Figure 1.
In healthy bone marrow (A), B-cells develop into antibody-producing plasma cells when foreign substances
(antigens) enter the body. Normally, plasma cells make up less than 1 percent of the cells in the bone marrow.
In multiple myeloma (B), genetic damage to a developing B cell transforms the normal plasma cell into a
malignant multiple myeloma cell. The malignant cell multiplies, leaving less space for normal blood cells in
the bone marrow, and produces large quantities of M protein.

A. Healthy

B. Multiple Myeloma

Genetic damage
B cell
Damaged B cell


Plasma cell

Figure 2.
Myeloma cells in the bone marrow cause osteolytic
lesions, which appear as holes on an x-ray.
Weakened bones increase the risk of fractures,
as shown in this x-ray of a forearm. DeVita VT Jr,
Hellman S, Rosenberg SA, eds. Cancer: Principles
and Practice of Oncology. 5th ed. 1997:2350. Adapted
with permission from Lippincott Williams & Wilkins.

Multiple Myeloma cell

Fracture caused
by lesion


Multiple Myeloma Disease Overview | 3

How Common Is Myeloma?

What Causes Myeloma?

Multiple myeloma is the second

To date, no cause for myeloma has

most common blood cancer, after non-

been identified. Research suggests

Hodgkins lymphoma, and represents

possible associations with a decline in the

approximately 1 percent of all cancers

immune system, some occupations,

and just under 2 percent of all cancer

exposure to certain chemicals and

deaths. The American Cancer Society

exposure to radiation. However, there are

estimates that multiple myeloma will be

no strong associations, and in most cases,

diagnosed in 21,700 people during 2012.

multiple myeloma develops in individuals

The number of cases of myeloma

who have no known risk factors.

reported at a particular time (prevalence)

Multiple myeloma may be the result

varies according to gender, age, and

of several factors acting together. It is

race or ethnicity. Multiple myeloma

uncommon for myeloma to develop in

is more common among men than

more than one member of a family.

women, occurs more frequently with

increasing age and develops twice

How Does Myeloma Affect

as often among black individuals than

the Body?

among white individuals.

The primary effect of multiple myeloma

is on the bone. The blood and the kidneys
are also affected (Figure 3).

4 | Multiple Myeloma Disease Overview

Figure 3. Effect of myeloma on major organs

in the body
The growing number of myeloma cells can interfere
with the production of all types of blood cells.
A reduction in the number of white blood cells can
increase the risk of infection, whereas decreased
red blood cell production can result in anemia.
A reduction in platelets can prevent normal blood
clotting. In addition, high levels of M protein and
light chains (portions of immunoglobulin molecules,
also known as Bence Jones proteins), crowd out
normal functioning immunoglobulins and thicken
the blood, causing additional symptoms.



Excess M protein and calcium in the blood

overwork the kidneys as they filter blood. The
amount of urine produced may decrease, and
the kidneys fail to function normally.

Myeloma cell damage leads to bone loss in two

ways. First, the cells gather to form masses in the
bone marrow that may disrupt the normal structure
of the surrounding bone. Second, myeloma cells
secrete substances that interfere with the normal
process of bone repair and growth. The most
commonly affected bones are the spine, pelvis, and
rib cage. Bone destruction can cause the level of
calcium in the bloodstream to rise, a condition called
hypercalcemia, which can be a serious problem if
appropriate treatment is not given immediately.

Multiple Myeloma Disease Overview | 5

What Are the Symptoms

In addition, symptoms related to high lev-

of Myeloma?

els of calcium in the blood (hypercalcemia)

There are often no symptoms in the

or kidney problems may include:

early stages of myeloma. When present,

symptoms may be vague and similar to

Increased or decreased urination

Increased thirst

Restlessness, eventually followed by

those of other conditions. Some of the

more common symptoms are:

Bone pain


extreme weakness and fatigue




Nausea and vomiting

What Tests Are Done to


Loss of appetite and weight loss

Diagnose Myeloma?
A number of laboratory tests are typically
carried out as part of an initial evaluation
to help confirm a diagnosis of myeloma.
These tests are done on samples of blood,
urine, bone, and bone marrow (Table 1).

6 | Multiple Myeloma Disease Overview

Table 1. common Laboratory Tests and Medical Procedures to

Confirm Diagnosis of Myeloma
Diagnostic Test



Complete blood count (number

Determine the degree to which

Low levels may signal anemia,

of red blood cells, white blood

myeloma is interfering with the

increased risk of infection and

cells, and platelets; and relative

normal production of blood cells

poor clotting

Chemistry profile (albumin,

Assess general health status and

Abnormal levels may indicate

calcium, lactate dehydrogenase

the extent of disease

kidney damage and increased

Blood Specimen

proportion of white blood cells)

size/number of tumors

[LDH], blood urea nitrogen [BUN]

and creatinine)
Beta2-microglobulin (2-M) level

C-reactive protein

Immunoglobulin levels

Determine the level of a serum

Higher levels indicate more

protein that reflects both disease

extensive disease; aids in

activity and renal function

staging of disease

Obtain an indirect measure of

Higher levels indicate more

the number of cancer cells

extensive disease

Define the levels of antibodies

Higher levels suggest the

that are overproduced by

presence of myeloma

myeloma cell
Detect the presence and

Higher levels indicate more

level of various proteins,

extensive disease; aids in

including M protein

classification of disease

Immunofixation electrophoresis

Identify the type of abnormal

Aids in classification of disease

(IFE; also called immunoelectro-

antibody proteins in the blood

Serum protein electrophoresis

phoresis )
Freelite serum free light

Measure immunoglobulin

Abnormal levels and/or ratio

chain assay

light chains

suggest the presence of

myeloma or a related disease

Table 1 continued on next page

Multiple Myeloma Disease Overview | 7

Table 1. (Continued) common Laboratory Tests and Medical

Procedures to Confirm Diagnosis of Myeloma
Diagnostic Test



Assess kidney function

Abnormal findings may

Urine Specimen

suggest kidney damage

Bence Jones protein level

Define the presence and level

Presence indicates disease,

(performed on 24-hour

of Bence Jones protein

and higher levels indicate

specimen of urine)
Urine protein electrophoresis

more extensive disease

Determine the presence and

Presence of M protein

levels of specific proteins in

or Bence Jones protein

the urine, including M protein

indicates disease

and Bence Jones protein

Bone/Bone Marrow Specimen

Imaging studies (bone [skeletal]

Assess changes in the bone

survey, x-ray, magnetic resonance

structure and determine the

imaging [MRI], computerized

number and size of tumors in

tomography [CT], positron

the bone

emission tomography [PET]*)

Biopsy (on either fluid aspirated

Determine the number and

Presence of myeloma cells con-

from the bone marrow or on

percentage of normal and

firms the diagnosis, and higher

bone tissue)

malignant plasma cells in the

percentage of myeloma cells

bone marrow

indicate more extensive disease

Cytogenetic analysis

Assess the number and normalcy

Loss of certain chromosomes

(e.g., fluorescence in situ

of chromosomes and identify the

(deletions) or translocations

hybridization [FISH])

presence of translocations (mis-

may be associated with poor

matching of chromosome parts)


*The clinical value of this test has not yet been determined.

8 | Multiple Myeloma Disease Overview

It is very important for you to have all

Seeing a Myeloma Specialist

the appropriate tests done, as the results

Once your doctor has diagnosed

will help your doctor to better determine

multiple myeloma, it is important that

treatment options and prognosis, or the

you consult a specialist experienced in

predicted course of disease and outcome.

treating myeloma to further evaluate

Many of these tests are also used to

your disease and help develop a treat-

assess the extent of disease and to plan

ment plan. You can usually find such a

and monitor treatment.

specialist at a National Cancer Institute

(NCI)-designated cancer center.

Cytogenetic analysis (analysis of the

chromosomes) is not routinely done for

Doctors usually refer individuals with

individuals with newly diagnosed

multiple myeloma to a hematologist/

myeloma, but is being performed more

oncologist, a doctor who specializes in

frequently at some medical institutions

blood diseases and disorders, as well

that specialize in the treatment of multiple

as cancer. Some hematologists/oncolo-

myeloma. How the results of cytogenic

gists further specialize in hematologic

analysis affect the selection of newer

cancers, such as multiple myeloma.

treatment agents is still evolving.

To find a cancer center or myeloma
Several genetic abnormalities have been

specialist, look in the Newly Diag-

identified in myeloma, and studies have

nosed Patients Section under Living

shown that response to treatment and

With Multiple Myeloma on the

prognosis may vary according to specific

MMRF Web site (

subtypes of the disease, but the con-

and go to Choosing Your Doctor.

nection has not been defined adequately

enough to aid in decision making about
the best treatment options.

Multiple Myeloma Disease Overview | 9

How Is Myeloma Classified

and Staged?
Myeloma is classified according to the
results of diagnostic testing, and these
results indicate whether or not immediate
treatment is needed. In addition, a stage is
assigned to denote the extent of disease.
Both staging and classification are useful
in determining treatment options.
Myeloma is classified into three categories (Table 2). Individuals in the first two
categories are considered asymptomatic
and do not have to receive anti-myeloma
treatment immediately. However, clinical
trials are being conducted to determine
if newer agents can delay disease progression and improve survival for this group
of individuals.

10 | Multiple Myeloma Disease Overview

Individuals with
myeloma are encouraged
to talk to their doctors
about participating in a
clinical trial.

Table 2. Classification of Multiple Myeloma




Monoclonal gammopathy

Considered a precursor

Close follow-up (also

of undetermined

to myeloma

significance (MGUS)

Blood M protein <3 g/dL and

known as observation)

Bone marrow plasma cells <10% and

No evidence of other B-cell disorders
No related organ or
tissue impairmenta
Risk of progression to malignancy:
1% per year (about 20%-25% of
individuals during their lifetime)
Asymptomatic, or

Blood M protein >3 g/dL and/or

smoldering, myeloma

Bone marrow plasma cells >10%

No related organ or tissue

Observation, with
treatment beginning at
disease progression

impairment or symptoms

Participation in a clinical trial

Risk of progression to

Treatment with

malignancy: 10% per year

bisphosphonates for individuals

with bone loss (osteoporosis
or osteopenia) similar to that
used for the treatment of
osteoporosis in general

Symptomatic myeloma

M protein in blood and/or urine

Immediate treatment

Bone marrow plasma cells

Treatment with

or plasmacytoma

bisphosphonates for individuals

Related organ or tissue impairment

with osteolytic lesions,

osteoporosis, or osteopenia
Participation in a clinical trial

Myeloma-related organ or tissue impairment (end-organ damage) includes hypercalcemia (increased blood
calcium levels), impaired kidney function, anemia, or bone lesions. These classifications are based on those
proposed by the International Myeloma Working Group.

Multiple Myeloma Disease Overview | 11


the number of osteolytic lesions, and the

The process of staging myeloma is

production rate of M protein (Table 3).

crucial to developing an effective treat-

Stages are further divided according to

ment plan. Historically, the system most

renal (kidney) function.

widely used has been the Durie-Salmon

Staging System, in which the clinical

A newer, simpler, more cost-effective

stage of disease (stage I, II, or III) is based

staging system that is being used

on four measurements: the hemoglobin

more often is the International Staging

value, the level of calcium in the blood,

System (ISS).

Table 3. The durie-salmon staging system



Myeloma Cell Massa

I (low cell mass)

All of the following:


Hemoglobin value >10 g/dL

Blood calcium value normal or <12 mg/dL
Bone x-ray, normal bone structure, or
solitary bone plasmacytoma only
Low M-protein production rate
(IgG value < 5 g/dL; IgA value <3 g/dL;
Bence Jones protein <4 g/24 hr.)
II (intermediate

Fitting neither stage I nor stage III


One or more of the following:


cell mass)
III (high cell mass)

Hemoglobin value <8.5 g/dL

Blood calcium value >12 mg/dL
Advanced lytic bone lesions
High M-protein production rate (IgG value
>7 g/dL; IgA value >5 g/dL; Bence Jones
protein >12 g/24 hr.)

The myeloma cell mass is expressed as the number of myeloma cells per body surface area.

Subclassification (either A or B)
A: Relatively normal renal function (blood creatinine value <2.0 mg/dL)
B: Abnormal renal function (blood creatinine value >2.0 mg/dL)

12 | Multiple Myeloma Disease Overview

The ISS was developed based on

may help in the treatment decision-

responses to front-line therapy with

making process. The ISS is useful only for

conventional chemotherapy and/or

individuals with symptomatic myeloma,

high-dose chemotherapy and stem cell

and its prognostic value when newer,

transplantation. The ISS is based on the

novel agents are used as front-line therapy,

assessment of two blood tests, beta2-

as well as following disease relapse

microglobulin (2-M) and albumin (Table 4).

(progression), is under investigation.

The three stages in this system indicate

different levels of projected survival and

Table 4. International Staging System for Myeloma

Stage Criteria

2-M <3.5 mg/L and albumin >3.5 g/dL

ll 2-M <3.5 mg/L and albumin <3.5 g/dL or 2-M 3.5 5.5 mg/L
lll 2-M >5.5 mg/L

2-M = beta2-microglobulin.

Multiple Myeloma Disease Overview | 13

Can Outcome Be Predicted?

What Are The Possible Goals

Several clinical and laboratory findings

of Treatment?

provide important information about

Depending on an individuals disease

prognosis (Table 5). These prognostic

and his or her wishes, treatment plans

indicators may also help decide when

may be designed to meet one or more

treatment should begin and aid in moni-

different goals (Table 6).

toring the disease. Many tests can be

performed routinely in any laboratory,
whereas others are performed only in specialized laboratories or a research setting.
Table 5. Prognostic Indicators


Values Indicating Lower

Risk at Diagnosisa

2-M level

<3.5 mg/mL

Higher levels reflect more extensive

disease and poor renal function

Albumin level

Higher levels may indicate a

>3.5 g/dL

better prognosis
Lactate dehydrogenase

Higher levels indicate more

Age <60 y: 100-190 U/L

(LDH) level

extensive disease

Age >60 y: 110-210 U/L

Chromosome analysis

Presence of specific abnormalities may

Absence of abnormalities

(cytogenetic testing,

indicate poor prognosis

by either karyotyping
or FISH)
Freelite serum free

Abnormal results indicate risk of

Free light chain ratio

light chain assay

progression of MGUS and smoldering

MGUS: 0.26-1.65

myeloma (SMM); as well as poorer

SMM: 0.125-8.0

prognosis in myeloma

Myeloma: 0.03-32

Gene expression

Presence of specific groups of genes can

Personalized risk score

profiling (Myeloma

predict low or high risk of early relapse

Prognostic Risk
SignatureTM MyPRSTM)

Note that these values are often different at other stages of the disease process, such as before or after stem
cell transplantation. These values may also be defined differently at different medical laboratories.

14 | Multiple Myeloma Disease Overview

How Do You Decide Which

Age and general health

Treatment is Appropriate?
Deciding on a particular treatment plan

n Symptoms

for myeloma is a complex process.

Treatment is tailored to each individual

Presence of disease complications

Prior myeloma treatment

The individuals lifestyle, goals, and

based on a number of things, including:


Results of the physical exam

Results of laboratory tests

The specific classification and stage

views on quality of life

of disease

Table 6. Treatment Goals

Goal Intervention/Requirement
Destroy all evidence of disease

May require use of aggressive treatment that

might have more severe side effects

Prevent damage to other organs of the body

Typically achieved with commonly used

by controlling disease activity

treatments that have side effects, but they are

acceptable and tolerable

Preserve normal performance and

May be possible with minimal treatment

quality of life for as long as possible

Provide lasting relief of pain and other disease

Involves use of supportive therapies that help

symptoms, as well as manage side effects

you feel better and manage complications

of treatment
Manage myeloma that is in remission

May involve long-term therapy

Multiple Myeloma Disease Overview | 15

Table 7. Therapies for Myelomaa



Velcade (bortezomib,

Proteasome inhibitor approved for use across the entire

Millennium: The Takeda

spectrum of myeloma disease

Oncology Company) for Injection


Oral agent that is an improvement over Thalomid and is effective across

(lenalidomide, Celgene)

the spectrum of myeloma disease; approved for use in combination

with dexamethasone in individuals who previously received treatment

KyprolisTM (carfilzomib.,

New type of proteasome inhibitor; approved for use in patients who have

Onyx Pharmaceuticals)

received at least 2 prior therapies including Velcade and an immunomodulatory agent (such as Revlimid or Thalomid)

Thalomid (thalidomide,

Oral agent shown to be effective across the spectrum of myeloma disease;


approved in combination with dexamethasone as front-line therapy.

Peripheral neuropathy is a common side effect and can be irreversible.

Doxil (doxorubicin HCl

Chemotherapy agent approved for use in combination with Velcade

liposome injection, Ortho Biotech)

for individuals who previously received therapy other than Velcade.

Side effects include mouth sores, swelling and blisters on the hands
or feet, and possible heart problems.

Steroids (corticosteroids)

Drugs used for decades to treat myeloma throughout the spectrum of

(dexamethasone and prednisone)

disease; may be used alone or in combination with other therapies.

How Do You Know if a

side effects. These tests also help

Treatment is Working?

determine if, after an initial response to

During and after treatment, your doctor

treatment, your myeloma relapses.

will monitor your levels of M protein and

your symptoms. Your doctor may also

In clinical trials, the outcome of treat-

perform some of the same laboratory

ment in myeloma is defined using very

tests and medical procedures that were

specific standards, or criteria. These

done when you were diagnosed with

response criteria allow the relative

myeloma, such as blood tests, x-rays or

effectiveness of one treatment to be

bone marrow biopsy. All of these results

compared with other treatments.

show how well the treatment is working

and whether you are experiencing any
16 | Multiple Myeloma Disease Overview



Conventional (standard

The use of drug(s), administered alone or in combination, to kill cancer

dose) chemotherapy

cells; some examples are melphalan (Alkeran, GlaxoSmithKline)

and cyclophosphamide

High-dose chemotherapy

The use of higher doses of chemotherapy drugs followed by

and stem cell transplantation

transplantation of hematopoietic stem cells to replace healthy

cells damaged by the chemotherapy.

Radiation therapy

The use of high-energy rays to damage cancer cells and prevent

them from growing

Supportive therapy

Therapies that alleviate symptoms and manage complications

of the disease and its treatment, such as bisphosphonates for
bone disease, low-dose radiation therapy and analgesics for pain
relief, growth factors, antibiotics, intravenous immunoglobulin,
orthopedic interventions, drugs (primarily anticoagulants) to
prevent and reduce the severity of deep vein thrombosis (DVT; blood
clots), antiemetics, and drugs to prevent and reduce the severity of
neuropathy (nerve damage)

Approved indications listed are those for the United States.

what therapies are used

of their effectiveness. Some treat-

in myeloma?

ments may be more potent against

Many therapies are available for myeloma

disease but cause more side effects.

(Table 7), and it is important to note that

In addition to treatment of the disease,

there is no one standard therapy for

supportive care is provided to alleviate

myeloma. The treatment approaches that

symptoms related to both the disease

are often referred to as standard are those

and its treatment.

used because of strong scientific evidence

Multiple Myeloma Disease Overview | 17

Figure 4. Treatment options for myeloma

Autologous stem cell transplant candidate?


Front-line therapy
Any of the following may be used:

Front-line therapy
Any of the following may be used:

Revlimid-VelcadeDexamethasone (RVD)
Revlimid-low-dose dexamethasone
MP-based regiments*
(Velcade-MP, Revlimid-MP
or MP-Thalomid)
Clinical trial

Revlimid-VelcadeDexamethasone (RVD)
Revlimid-low-dose dexamethasone
Velcade-dex or other
Velcade-based regimen
Clinical trial
Continue until
plateau; delayed
upon relapse


Response to front-line therapy?

Continue with either:
Maintenance therapy


No response or relapse
Second-line therapy
If no response, or
If relapse occurs
if soon after initial
after a period of
therapy, use a
response to initial
different agent(s)
therapy, may repeat
than that used for
the initial therapy
initial therapy

Revlimid- or Velcade-based regimen

Velcade + Doxil
Second transplant if stem cells
available/harvest possible
Clinical trial

No response or relapse
Third-line therapy

*Primarily used outside the US

MP = Melphalan - Prednisone
18 | Multiple Myeloma Disease Overview

Kyprolis (if previously received Velcade

and Revlimid or Thalomid)
Use different agent(s) than that used for
initial or second-line therapy
Clinical trial

Initial Therapy for

Increasingly, patients who were not

Newly Diagnosed

candidates for transplant are being

Symptomatic Disease

treated with the same drug regimens

In the past, initial treatment options were

as transplant candidates.

based on whether or not a patient was a

candidate for high-dose chemotherapy and

Treatment options for initial therapy include:

autologous stem cell transplantation.

Today, the majority of treatments may

Revlimid-Velcade-dex (RVD)

Revlimid-low-dose dexamethasone

Velcade-based regimens, such as

be appropriate regardless of whether or

not a patient is a candidate for transplant.
In addition to specific treatment aimed
at stopping the progression of disease,


individuals with myeloma may receive

supportive care, such as intravenously
administered bisphosphonates to relieve

MP-based regimens (Velcade-MP,

MP-Revlimid, MP-Thalomid)

bone pain and reduce the risk of fracture,

blood transfusions or treatments (such
as erythropoietin) to treat anemia due

Investigational regimen in a clinical trial

to chemotherapy, drugs to strengthen

immunity, and antibiotics to treat infection.

Notably, MP-based regimens are primarily

Participation in a clinical trial is an option at

used outside of the US.

virtually every stage of the disease.

You and your doctor will discuss the treatIt is important to note that the order of

ment regimen that is right for you.

treatment options listed here does not

imply degree of effectiveness.

Initial therapy for myeloma is continued

for about a year or until the response of

Individuals Who Are Not Candidates

the disease to the treatment reaches a

for a Transplant

plateau, or levels off. At that time, the

Advances in myeloma research have

individual may be followed-up closely with

expanded the treatment options for indi-

no therapy (often referred to as observa-

viduals who are not candidates for stem

tion) or the doctor may ask the individual

cell transplantation.

to consider maintenance therapy, which

may also be done with the patient participating in a clinical trial.

Multiple Myeloma Disease Overview | 19


Individuals Who Are Candidates for


a Transplant

The improved response rates that have

Stem cell transplantation involves the use

been found with use of newer agents

of higher than conventional doses of che-

as initial therapy have raised questions

motherapy, and the stem cells provided by

about the role of transplantation in the

the transplant replace normal cells dam-

treatment of myeloma.

aged by the chemotherapy. This approach

offers a chance for a good response and

Preliminary results from several studies

survival, but the individual must be able

appear to indicate that transplantation

to tolerate the side effects of the higher

remains a standard therapy and may

doses of chemotherapy. Therefore, poten-

improve outcomes when compared to

tial candidates must be in good physical

standard therapy with newer agents.

condition, with adequate kidney, lung and

However, longer follow-up is needed

heart function. (See page 21 for more

in order to compare survival, and the

information about stem cell transplantation.)

potential toxicities associated with

transplantation must be balanced with

Induction Therapy

the benefits.

Before the transplant is done, initial

treatment, referred to as induction ther-

Until then, people with myeloma

apy, is given to reduce the amount of

should carefully discuss the benefits

myeloma cells. For the most part, options

and risks of all treatment options with

for transplant candidates are similar to

their doctors. All individuals who are

those for non-transplant candidates.

eligible for transplantation are encour-

However, transplant candidates need to

aged to have stem cells obtained (also

avoid the use of melphalan and prolonged

known as harvested) so that the

use of Revlimid before stem cell mobi-

cells are available if the individual later

lization, as these agents may impair the

chooses to undergo transplantation.

ability to collect stem cells. Treatment

options include:
n Revlimid-Velcade-dexamethasone

Revlimid-low-dose dexamethasone

Velcade-dex and other

Velcade-based regimens

20 | Multiple Myeloma Disease Overview

Because prolonged use of melphalan may

Figure 5. Stem cell transplantation

impair the ability to collect stem cells for

1. Collection

use in a transplant, other agents are typi-

In stem cell transplantation, peripheral blood stem

cells (PBSCs) are collected (also called harvested)
from the individual with myeloma following
administration of growth factors with or without
chemotherapy, or from a donor.

cally used as initial induction therapy.

Participation in a clinical trial, such as
one evaluating an investigational induction regimen, is also an appropriate option
for patients considering a transplant.

Stem cells

Stem Cell Transplantation

Stem cells are normally found in the
bone marrow and in the peripheral blood
(blood found in the arteries or veins).
Virtually all transplants in myeloma are

2. High-dose chemo

now obtained from the peripheral blood

The cells are processed in the laboratory, frozen, and

stored until needed. The person receives high-dose

and are referred to as peripheral blood

stem cell (PBSC) transplants.
Stem cell transplantation is done after
completion of induction therapy. With an
autologous transplant, the individuals stem
cells are collected (also called harvested)
and are reintroduced following high-dose
chemotherapy (Figure 5). An allogeneic
transplant involves collecting stem cells

3. Infusion
The stem cells are then thawed and infused into the
individual with myeloma.

from a donor (usually a relative of the individual with myeloma) and infusing them
into the individual after high-dose therapy.

Stem cells

This type of transplant is infrequently performed today because of the high risk of
complications. A mini (nonmyeloablative)
allogeneic transplant is a modified form of
allogeneic transplant in which a lower dose

Transplanted stem cells begin to produce new

blood cells.

of chemotherapy is used.

Multiple Myeloma Disease Overview | 21


Treatment Options


for Relapsed or

There is increasing evidence supporting

Refractory myeloma

the role of maintenance therapy after the

If relapse occurs after a period of initial

completion of front-line therapy alone or

response to therapy, the initial therapy

after front-line therapy and transplanta-

may be repeated. Alternatively, another

tion. Because myeloma is not curable, it

regimen commonly used as initial therapy

will recur even in individuals who initially

may be given. Participation in a clinical trial

respond to treatment. The overall goal of

is also an option.

maintenance therapy is to maintain the

response for as long as possible, thus

Individuals who relapse shortly following

improving survival.

completion of initial therapy may no longer

respond to the initial medications used.

The results of studies are now showing

These individuals, as well as those who

that maintenance therapy may improve

do not respond to initial therapy, are said

survival and help to keep myeloma in

to have refractory disease. As with the

remission after transplantation, and sug-

primary treatment of myeloma, recent

gest it also provides benefit for patients

advances in research have created more

who have not received a transplant. Two

options for treating relapsed/refractory

large trials showed that Revlimid provides

disease. These options include:

significant benefit as maintenance therapy

after transplantation, with one study dem-

A variety of approved agents, including

onstrating improved survival. Researchers

Revlimid-dex, Velcade (with or without

are evaluating other regimens, including

dex), Velcade-Doxil, Thal-dex, and con-

Thalomid (alone or in combination with dex

ventional chemotherapy agents such as

or prednisone) or Velcade (alone or with

melphalan and cyclophosphamide

Thalomid). While more data are needed to

definitively determine the survival benefit

Kyprolis, which is a new type of

of maintenance therapy, more doctors are

proteasome inhibitor approved for use

likely to discuss the benefit and risk of

in patients who have received at least

maintenance therapy with their patients

two prior therapies including Velcade

based on these promising results.

and an immunomodulatory agent (such

as Revlimid or Thalomid)

22 | Multiple Myeloma Disease Overview

Various published multi-drug

combination regimens based on
novel therapies with or without
steroids and/or chemotherapy

Stem cell transplant (if possible)

Participation in a clinical trial

Participating in a clinical trial offers

access to the very latest advances in
treatment. The MMRF Patient Navigator
Program matches individuals with appro-

You can call 866.603.MMCT

(6628) to speak with a
Clinical Trials Specialist
who will ask you questions
and talk to you about
clinical trials that will be
appropriate for you. The
Specialist can also help
you become enrolled in a
trial if that is your choice.

priate clinical trials. To take advantage of

this program, you (or your caregiver or

Weblinks: Clinical Trial Information

family member) can complete a simple

MMRF Patient Navigator Program

questionnaire online.

What Does the Future Look

Like for Myeloma Treatments?
Current myeloma research focuses on
the development of newer agents and
the evaluation of current drugs in new
combinations to determine the optimal
combination and the best sequencing
of treatment. As research in myeloma
evolves, newer treatment options have
the potential to substantially improve
survival and quality of life.
We would like to thank
Ravi Vij, M.D. for his
contributions to this brochure.

Multiple Myeloma Disease Overview | 23

Questions to Ask Your Doctor

1 Should I be treated now or should therapy be delayed?


What is the expected outcome of the treatment? What are the goals of

this therapy (is it given primarily to treat the disease or to relieve symptoms)?

What is the recommended treatment? Is it a single drug or a combination

of drugs? How is the drug administered: orally or intravenously (by IV)?

How long is treatment given? How will I be monitored?

Am I a candidate for stem cell transplantation? If so, what kind autologous

or allogeneic?

How likely is a complete or partial remission? What factors contribute to

better or worse odds?

How will I feel during and after treatment? What kinds of side effects might

I expect? What should I do if I experience side effects? What kind of impact

will treatment have on my daily life?

How long is the typical recovery time? Is there any follow-up or

maintenance therapy?

What is the cost of therapy? What costs will my insurance cover and what

costs will I have to pay?

9 What are the alternatives to this treatment? How do the different therapies
(standard and alternative) compare with respect to effectiveness and side effects?
10 Are there any clinical trials that are appropriate for me? If so, what is
involved? What are the potential risks and benefits? What are the costs?
11 If one or more types of treatment fails, what are my options?

24 | Multiple Myeloma Disease Overview


Beta2-microglobulin (2-microglobulin

Albumin Major protein found in the

or 2-M) A protein normally found on

blood. A persons albumin level can

the surface of various cells in the body.

provide some indication of the overall

Increased blood levels occur in inflamma-

health and nutritional status.

tory conditions and certain lymphocyte

disorders, such as myeloma.

Allogeneic transplant Stem cell transplant in which cells are collected from

Bisphosphonate Type of drug used to

another person.

treat osteoporosis and bone disease in

individuals with cancer. Bisphosphonates

Anemia A decrease in the number of

work by inhibiting the activity of bone-

red blood cells in the blood.

destroying cells (osteoclasts).

Antibody Protein produced by plasma

Blood urea nitrogen (BUN) A byproduct

cells that helps protect the body from

of protein metabolism that is normally

infection and disease. Also called immuno-

filtered out of the blood and found in the

globulin (Ig).

urine. Elevated levels in the blood can indicate decreased kidney function.

Anticoagulant Drug that prevents blood

from clotting.

Bone marrow Soft, spongy tissue found

in the center of many bones where blood

Antiemetic Drug that prevents or

cells are produced.

alleviates nausea and vomiting.

Bone (skeletal) survey A series of x-rays
Autologous transplant Stem cell

of the skull, spine, arms, ribs, and legs.

transplant in which cells are collected

from the individual being treated.

C-reactive protein (CRP) A protein

produced by the liver when there is an

B cell Also called a B lymphocyte. White

inflammatory process occurring in the

blood cell that gives rise to a plasma cell.

body. Serum levels of CRP are increased

in myeloma, as well as in various inflam-

Bence Jones protein A short (light chain)

matory and degenerative diseases and

protein that is produced by myeloma cells.

other types of cancer.

Multiple Myeloma Disease Overview | 25

Calcium Mineral important in bone

Electrophoresis Laboratory test used

formation. Elevated serum levels occur

to measure the levels of various proteins

when there is bone destruction.

in the blood or urine. Uses an electrical

current to sort proteins by their charge.

Chemotherapy The use of drugs to kill

rapidly dividing cancer cells.

Erythropoietin Growth factor that

stimulates the bone marrow to produce

Chromosome A thread-like

red blood cells.

structure in a living cell that contains

genetic information.

Front-line therapy The initial treatment

given (also known as first-line therapy).

Complete blood count (CBC) Blood test

that measures the number of red blood

Fluorescence in situ hybridization

cells, white blood cells, and platelets in

(FISH) A laboratory technique used to

the blood and the relative proportions of

determine how many copies of a specific

the various types of white blood cells.

segment of DNA are present or absent

in a cell.

Computerized tomography (CT)

Imaging technique that uses a computer

Gene expression profiling A test that

to generate three-dimensional x-ray pic-

provides a genetic fingerprint of a

tures. Also referred to as computerized

cancer. The genetic fingerprint can provide

axial tomography (CAT).

an estimate on the risk of relapse.

Corticosteroids A potent class of drugs

Growth factor Substance that stimulates

that have anti-inflammatory, immuno-

cells to multiply.

suppressive, and antitumor effects.

Dexamethasone and prednisone are

Hematocrit Proportion of blood that

examples of corticosteroids.

consists of red blood cells.

Creatinine A product of energy metabo-

Hemoglobin Oxygen-carrying substance

lism of muscle that is normally filtered

in red blood cells.

out of the blood and found in the urine.

Elevated levels in the blood can indicate
decreased kidney function.

26 | Multiple Myeloma Disease Overview

Hematopoietic stem cell Parent cell

Lymphocyte Small white blood cell

that grows and divides to produce red

essential for normal function of the

blood cells, white blood cells, and plate-

immune system; may be one of two

lets. Found primarily in the bone marrow

types: a T lymphocyte or B lymphocyte.

but also in the peripheral blood.

(Hematopoietic stem cells are different

Magnetic resonance imaging (MRI)

from embryonic stem cells.) See also

Imaging technique that uses magnetic

stem cell transplantation.

energy to provide detailed images of

bone and soft tissue.

Hypercalcemia Condition noted by

elevated levels of calcium in the blood

Malignant Cancerous.

due to increased bone destruction.

Monoclonal gammopathy of
Immunofixation electrophoresis (IFE)

undetermined significance (MGUS)

Type of electrophoresis that uses a special

A precancerous and asymptomatic

antibody staining technique to identify

condition noted by the presence of

specific types of immunoglobulins; also

M protein in the serum or urine. MGUS

called immunoelectrophoresis.

may progress to myeloma.

Immunoglobulin (Ig) See antibody.

Monoclonal (M) protein Abnormal

antibody (immunoglobulin) found in

Induction therapy Treatment used as a

large quantities in the blood and urine

first step in shrinking the cancer and in

of individuals with myeloma.

evaluating response to drugs and other

therapeutic agents.

Neuropathy Disorder of the nerves

that can result in abnormal or decreased

Lactate dehydrogenase (LDH) An

sensation, or burning/tingling. When the

enzyme found in body tissues. Elevated

hands and feet are affected, it is referred

blood levels occur when there is tissue

to as peripheral neuropathy.

damage and may occur in myeloma,

where they reflect tumor-cell burden.

Osteolytic lesion Soft spot in the bone

where bone tissue has been destroyed.

Light chains Short protein chains

The lesion appears as a hole on a standard

on immunoglobulins.

bone x-ray.

Multiple Myeloma Disease Overview | 27

Osteopenia Condition of decreased

Red blood cell Oxygen-transporting

bone density.

blood cell.

Osteoporosis Generalized bone loss

Refractory disease Disease that is not

typically associated with old age, but

responsive to therapy.

which can also occur in myeloma.

Relapse Return of disease or disease
Plasma cell Antibody-secreting immune


cell that develops from a B cell.

Second-line therapy Treatment that
Plasmacytoma Single tumor comprised

is given after failure of front-line

of malignant plasma cells that occurs in

therapy (disease is refractory) or after

bone or soft tissue. Myeloma may develop

disease relapses.

in patients with a plasmacytoma.

Stem cell transplantation Therapeutic
Platelets Small cell fragments in the blood

procedure in which bone marrow or

that help it to clot.

peripheral blood stem cells are collected,

stored, and infused into an individual

Positron emission tomography (PET)

following high-dose chemotherapy to

Imaging technique in which radioactive

restore blood cell production.

glucose (sugar) is used to highlight

cancer cells.

White blood cell One of the major cell

types in the blood; attack infection and

Prognosis The predicted course of a

cancer cells as part of the immune sys-

disease and the outcome after treatment.

tem. Lymphocytes are a type of white

blood cell. Also called a leukocyte.

Proteasome Complex of enzymes

that plays a role in the regulation of
cell function and growth by breaking
down proteins in a cell after they have
performed their functions, allowing
various cellular processes to continue
in an orderly fashion.

28 | Multiple Myeloma Disease Overview


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