Multiple Myeloma | Cancer of the Bone Marrow

Concise
Review
of Relapsed Myeloma
July 2023 Edition | Prepared by Brian G.M. Durie, MD

A publication of the International Myeloma Foundation

Founded in 1990, the International Myeloma Foundation (IMF)
is the first and largest organization focusing specifically on
myeloma. The IMF’s reach extends to more than 525,000
members in 140 countries. The IMF is dedicated to improving
the quality of life of myeloma patients while working toward
prevention and a cure through our four founding principles:
Research, Education, Support, and Advocacy.

RESEARCH The IMF is dedicated to finding a cure for myeloma, and we have a
range of initiatives to make this happen. The International Myeloma Working Group,
which emerged from the IMF’s Scientific Advisory Board established in 1995, is the
most prestigious organization with nearly 300 myeloma researchers conducting
collaborative research to improve outcomes for patients while providing critically
appraised consensus guidelines that are followed around the world. Our Black Swan
Research Initiative® is bridging the gap from long-term remission to cure. Our annual
Brian D. Novis Research Grant Program is supporting the most promising projects
by junior and senior investigators. Our Nurse Leadership Board, comprised of nurses
from leading myeloma treatment centers, develops recommendations for the
nursing care of myeloma patients.

EDUCATION The IMF’s webinars, seminars, and workshops provide up-to-date

information presented by leading myeloma scientists and clinicians directly to patients
and their families. We have a library of more than 100 publications for patients, care
partners, and healthcare professionals. IMF publications are always free-of-charge,
and available in English and select other languages.

SUPPORT The IMF InfoLine responds to your myeloma-related questions and

concerns via phone and email, providing the most accurate information in a caring
and compassionate manner. We also sustain a network of myeloma support groups,
training hundreds of dedicated patients, care partners, and nurses who volunteer
to lead these groups in their communities.

ADVOCACY We empower thousands of individuals who make a positive impact

each year on issues critical to the myeloma community. In the U.S., we lead coalitions
to represent the interests of the myeloma community at both federal and state levels.
Outside the U.S., the IMF’s Global Myeloma Action Network works to help patients
gain access to treatment.
Learn more about the ways the IMF is helping
to improve the quality of life of myeloma patients
while working toward prevention and a cure.
Call us at 1.818.487.7455 or 1.800.452.CURE,
or visit myeloma.org.
Contents

You are not alone 4

What you will learn from this booklet 4

Epidemiology 5

Clinical features of myeloma 7

Pathophysiology 12

Response or remission 16

Relapsing or refractory myeloma 18

Drugs in use for myeloma 27

Clinical trials 30

Supportive care 30

In closing 32

Terms and definitions 32

 You are not alone
The International Myeloma Foundation is here to help you. The IMF
is committed to providing information and support for patients with
multiple myeloma (which we refer to simply as “myeloma”) and their
care partners, friends, and family. We achieve this through a broad range
of resources available on our website myeloma.org, the IMF InfoLine,
seminars, webinars, workshops, and other programs and services.

What you will learn from this booklet

Myeloma is a cancer that is not known to most patients at the time of
diagnosis. To play an active role in your own medical care and to make
good decisions about your care with your doctor, it is important and
helpful to learn about this disease, as well as its treatment options and
supportive care measures.
The information in this booklet can guide you in your discussions with
your doctor. It is not intended to be a substitute for medical advice. Your
doctor is best able to answer questions about your specific healthcare
management plan.
The IMF Concise Review of the Disease and Treatment Options is an overview
of myeloma for patients with relapsed or refractory disease. It includes
a discussion of epidemiology, clinical features, pathophysiology, drugs
currently in use for myeloma in the U.S., response or remission, relapsing
or refractory disease, and supportive care.
If you are newly diagnosed with myeloma, we suggest that you first read
the IMF’s publication Patient Handbook for the Newly Diagnosed, which
will help you to better understand this complex disease, its possible causes
or triggers, diagnostic criteria, staging, types of myeloma, its effects inside
and outside the bone marrow, treatment for newly diagnosed myeloma,
and supportive care.
If you have been diagnosed with an asymptomatic precursor condition and
not with active myeloma, read the IMF’s publication Understanding MGUS
and Smoldering Multiple Myeloma.
If you are a myeloma patient in the United States who is in discussions with
your treating doctors about the possibility of having an autologous stem
cell transplant (ASCT) as part of your overall treatment strategy, read the
IMF’s publication Understanding Stem Cell Transplant in Myeloma.
Words in bold+blue type are explained in the “Terms and definitions”
section at the end of this booklet. The IMF’s Glossary of Myeloma Terms
and Definitions, a more complete myeloma-related compilation, is located
at glossary.myeloma.org.

4 1.818.487.7455 • 1.800.452.CURE
If you are reading this booklet in electronic format, the light blue links
will take you to the corresponding resources. All IMF publications are
free-of-charge and can be downloaded or requested in printed form
at publications.myeloma.org.

Epidemiology
In the United States, according to data from the Surveillance, Epidemiology,
and End Results (SEER) program of the National Cancer Institute (NCI)
at seer.cancer.gov 35,730 new cases of myeloma are estimated for 2023,
representing 1.8% of all new cancer
Figure 1. Myeloma cells
cases. According to the latest SEER
in the bone marrow
data available at this time, there
were an estimated 170,405 people
living with myeloma in the US
in 2020.
As published in the journal
Oncologist in 2020, the global
incidence of myeloma shows
significant disparities, indicating
under-recognition and suboptimal
treatment in many parts of the
world. The article highlights the
importance of economic resources,
access to and quality of healthcare,
and patient education for improving
diagnosis and survival of patients
with myeloma worldwide.
Myeloma is most frequently diagnosed in individuals who are 65–74 years
old, but it is also being diagnosed in people younger than 50. Only 5%–10%
of myeloma patients are under the age of 40. Myeloma in children is
extremely rare.
Men are more likely than women to develop myeloma. The disease is twice
as common in people of African descent. It appears that the incidence of
myeloma is increasing in several parts of the world, especially in Asia.
Approximately 5%–7% of myeloma diagnoses occur in individuals with a
close relative diagnosed with MGUS, SMM, or myeloma. If you have a close
relative with such a diagnosis, tell your primary care doctor to include this
information in your medical record. Conversely, tell your relatives to inform
their doctors to include your diagnosis in their medical history if you have
MGUS, SMM, or myeloma.

myeloma.org 5
 Figure 2. Disease phases

Asymptomatic Symptomatic

Active
M-proteins (g/dL)

myeloma
Relapse Refractory
relapse
MGUS or
smoldering
myeloma Plateau
Remission
Therapy

Time

Table 1. IMWG Diagnostic Criteria

DISORDER DEFINITION
MGUS All criteria must be met
1. Presence of M-protein in the serum < 3 g/dL,
2. P resence of monoclonal plasma cells in the bone marrow < 10%, and
3. Absence of CRAB criteria – elevated Calcium, Renal (kidney) damage,
Anemia, or Bone disease.
Light chain All criteria must be met
MGUS 1. Abnormal FLC ratio < 0.26 or > 1.65,
2. L evel of the appropriate involved light chain (increased kappa FLC in patients
with ratio > 1.65 and increased lambda FLC in patients with ratio < 0.26),
3. No Ig heavy chain expression on immunofixation,
4. A bsence of CRAB criteria,
5. Presence of monoclonal plasma cells in the bone marrow < 10%, and
6. Presence of M-protein in the urine based on a 24-hour collection < 500 mg.
SMM Both criteria must be met
1. Presence of M-protein in the serum (IgG or IgA) ≥ 3 g/dL, or urinary
M-protein ≥ 500 mg per 24-hour collection, and/or presence of monoclonal
plasma cells in the bone marrow 10%–60%, and
2. A bsence of myeloma-defining events (MDE) or amyloidosis.
Myeloma Both criteria must be met
1. Presence of monoclonal plasma cells in the bone marrow ≥ 10%,
or biopsy-proven bony or extramedullary plasmacytoma, and
2. A ny one or more of the following myeloma-defining events (MDE):
 Presence of CRAB criteria,
 Presence of monoclonal plasma cells in the bone marrow ≥ 60%,
 Ratio of involved-to-uninvolved serum FLC ≥ 100
(involved FLC level must be ≥ 100 mg/L and urine M-protein level
must be at least 200 mg per 24-hour collection on UPEP),
 One or more focal lesions on MRI studies (at least 5mm in size),
 One or more osteolytic lesions on skeletal radiography, CT, or PET-CT
Modified from Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for
the diagnosis of multiple myeloma. Lancet Oncology 2014.

6 1.818.487.7455 • 1.800.452.CURE
 Figure 3. Structures of immunoglobulins

IgG, IgE, IgD IgA

IgM

Clinical features of myeloma

Myeloma is a cancer of the bone marrow plasma cells, white blood cells
(WBC) that make antibodies, also called immunoglobulins (Ig). Healthy
plasma cells are an important part of the immune system. Myeloma
cells are malignant (cancerous) plasma cells that do not make functioning
antibodies, but instead produce an abnormal monoclonal protein
(myeloma protein, M-protein).
Myeloma has been recognized since Ancient Times. In 1844, in his
description of a case of myeloma, Dr. Samuel Solly referred to “soft
and fragile bones.” In 1845, the first well-documented patient, Thomas
Alexander McBean, was diagnosed by Dr. William Macintyre. In 1846,
Dr. John Dalrymple determined that the diseased bones contained cells
subsequently shown to be plasma cells. The unusual urine problem
discovered by Dr. Macintyre was investigated by Dr. Henry Bence Jones,
who published his findings in 1848.
Figure 4. Immunoglobulin molecule structure

Variable region Light chain

Antigen Constant
region Heavy
binding
CL CL chain

Fab Interchain
disulfide
CH1 bonds CH1

Hinge region
Biologic CH2 Complement-binding
activity region
mediation
Fc CH3 Binds to Fc receptor

myeloma.org 7
 Figure 5. Healthy bone compared
to bone damaged by myeloma
HEALTHY BONE
MULTIPLE MYELOMA
- accumulation of malignant
+
In 1873, Johann von Rustizky
introduced the term “multiple
myeloma” to designate the
presence of multiple plasma cell
lesions in bone. In 1889, Otto
Kahler published a detailed
clinical description of “Kahler’s
disease” (multiple myeloma). The
routine diagnosis of myeloma
remained difficult until bone
marrow aspiration began to
be used on a broader scale in
the 1930s.
The major features of myeloma
result from the abnormal

(cancerous) plasma cells within

the bone marrow. Known as the
© 2017 Slaybaugh Studios

Lytic Myeloma “CRAB criteria,” these features

lesion cells
include an elevated level of
calcium in the blood, renal
(kidney) damage, anemia or
low red blood cell count, and
Figure 6. Bone marrow aspiration bone damage are criteria used
to diagnose myeloma along
Site of biopsy with “Myeloma-defining event
(MDE).”
¡ Disruption of normal
bone marrow function
reflected by anemia, low
white blood cell (WBC) count,
Skin and/or low platelet count
(thrombocytopenia).
Bone
¡ Invasion and destruction of
bone and areas surrounding
Bone
the bone marrow involvement.
marrow
¡ Production and secretion
© 2015 Slaybaugh Studios

(release) of monoclonal
protein from the myeloma
cells into the bloodstream
and/or into the urine.

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 ¡ Reduction of normal immune function, reflected by reduced levels
of normal immunoglobulins and increased susceptibility to infection,
which is more likely if the WBC count is low.
Plasmacytomas are localized tumors composed of plasma cells, which
can grow inside bone (intramedullary) or outside bone (extramedullary,
soft-tissue). When there are multiple plasmacytomas, this condition is also
called myeloma.
Production and release of M-protein
The amount of M-protein produced by myeloma cells varies from patient
to patient. It is very important to determine if a patient’s myeloma
cells are high producers of M-protein, low producers (hyposecretory
or oligosecretory myeloma), or non-secretory. Approximately 1% of
myeloma patients do not have detectable M-protein in the blood and
urine. Some of these patients can be
successfully monitored using the serum Table 2. Types of M-protein (%)
free light chain (FLC) assay; others
% Totals
may be monitored with bone marrow
biopsy and/or PET-CT scan. The myeloma 1. Serum
therapies used for patients with non- IgG 52
secretory myeloma are the same as those
used for patients who secrete detectable IgA 21 75%
levels of M-protein. IgD 2

Once the relationship between the IgE < 0.01

M-protein level and the amount of 2. IgM (rarely myeloma,
myeloma in the bone marrow is known, typically associated
12%
it is possible to interpret and understand with Waldenström’s
the relationship between a particular macroglobulemia)
protein level and the myeloma tumor 3. Urine types κ and λ
burden. The M-spike that occurs on protein (Bence-Jones proteins 11%
electrophoresis laboratory tests is a or light chains only)
marker for the activity of myeloma cells. 4. Two or more
<1
M-proteins
The M-protein is an immunoglobulin or
a fragment of an immunoglobulin. In Heavy chains 2%
<1
myeloma cells, mutations have occurred (G or A) only
in the genes responsible for immunoglob- No M-protein 1
ulin production, and the M-proteins have
Total 100%
an abnormal amino acid sequence and
protein structure. Typically, the normal * This includes different types of myeloma,
MGUS, as well as Waldenström macroglob-
antibody function of the immunoglobulin ulemia (per data collected and analyzed by
is lost, and the 3-dimensional structure of W Pruzanski and MA Ogryzlo, 1970).

myeloma.org 9
 Table 3. Medical problems related to myeloma

EFFECTS OF INCREASED CAUSE IMPACT ON PATIENT

MYELOMA CELLS
IN BONE MARROW
CRAB criteria

C – Increase in Release of calcium from damaged • Mental confusion

blood Calcium bone into bloodstream. • Dehydration
• Constipation
• Fatigue
• Weakness
• Renal (kidney) damage

R–R
 enal problems – Abnormal M-proteins produced by • Sluggish circulation
kidney damage the myeloma cells are released into • Fatigue
the bloodstream and can pass into • Mental confusion
the urine, causing kidney damage.
High blood calcium, infections,
and other factors can also cause
or increase the severity of kidney
damage.

A – Anemia Decrease in number and activity of • Fatigue

red blood cell-producing cells in the • Weakness
bone marrow.

B – Bone Damage The myeloma cells activate • Bone pain

• Thinning osteoclast cells, which destroy bone • Fracture or collapse of a bone
(osteoporosis) or and block osteoblast cells, which • Bone swelling
• Areas of more severe normally repair damaged bone. • Nerve or spinal cord damage
damage (called lytic
lesions), fracture, or
collapse of a vertebra

Additional types of Local or systemic effects of • Neuropathy

organ dysfunction myeloma, other than CRAB features. • Recurrent infections
• Bleeding problems
• Other individual problems

Abnormal immune The myeloma cells reduce the • Susceptibility to infection

function number and activity of normal • Delayed recovery
plasma cells capable of producing from infection
antibodies against infection.

10 1.818.487.7455 • 1.800.452.CURE
 the molecule may be abnormal. Figure 7. SPEP test results
Increased production of abnor-
albumin
mal immunoglobulin results in
the following:
¡ Excess M-protein accumulates
in the bloodstream and/or is
excreted in the urine.
¡ The abnormal monoclonal alpha-1 alpha-2 beta-1 beta-2 gamma
molecules can adhere to each
other and/or to other tissues Normal SPEP result
(e.g., blood cells, blood vessel
albuminwalls, and other blood compo- albumin
nents). This can reduce blood beta-2
flow and circulation, causing
hyperviscosity syndrome
(HVS). It is important to be
aware that routine blood
testing
alpha-1 alpha-2 can
beta-1give
beta-2very
gammastrange alpha-1 alpha-2 beta-1 gamma
results due to hyperviscosity
of myeloma blood samples in
Abnormal result with myeloma cells producing
automated chemical analyzers the M-protein, creating an M-spike
or because of interference in the beta-2 region
with chemical reactions.
albumin albumin
¡ More light chains are gamma
beta-2
produced than are needed
to combine with the heavy
chains to create a whole
immunoglobulin molecule.
These excess light chains are
alpha-1 alpha-2 beta-1 gamma alpha-1 alpha-2 beta-1 beta-2
called Bence-Jones proteins.
Free Bence-Jones proteins
have a molecular weight of Abnormal result with myeloma cells producing
the M-protein, creating an M-spike
22,000 daltons and are small in the gamma region
enough to pass into the urine.
¡ The abnormal M-proteins can also have a wide range of other
properties including:
¡ Binding to normal blood clotting factors, resulting in increased
bleeding tendency, enhanced blood clotting, or phlebitis
(inflammation of a vein).
¡ Binding to nerves to cause neuropathy, or to circulating hormones
to cause metabolic dysfunction.

myeloma.org 11
 ¡ Free Bence-Jones proteins can adhere to each other or to other
tissues – same as an immunoglobulin molecule – and may cause
one of the following:
¡A
 myloid lightchain (AL) amyloidosis
AL amyloidosis is a plasma cell disorder in which light chain
proteins are not excreted by the kidneys, but become crosslinked
with each other, and these amyloid fibrils are then deposited in
tissues and organs.
¡M
 onoclonal immunoglobulin deposition disease (MIDD)
MIDD is caused by deposition of heavy chains, light chains, or both
heavy and light chains in organs. MIDD usually affects the kidneys
but can affect other organs, and the goal of treating MIDD is to
slow damage to organs.
 Light chain deposition disease (LCDD) is a type of MIDD,
characterized by deposition of complete or partial monoclonal
light chains in organs.
 Heavy chain deposition disease (HCDD) is a type of MIDD,
characterized by deposition of monoclonal heavy chains
in organs.

Pathophysiology
The uncontrolled growth of myeloma cells has many consequences,
including skeletal destruction, increased plasma volume and viscosity,
suppression of normal immunoglobulin production, and renal (kidney)
insufficiency. Nonetheless, the disease can be asymptomatic for many years.
With symptomatic myeloma, the most common presenting complaint is
bone pain. The serum and/or urine M-protein is elevated and typically rising
at the time of diagnosis.
Hypercalcemia
Calcium is a mineral found mainly in the hard part of bone matrix
(hydroxyapatite). If produced or released in excess, it can build up in the
bloodstream. Hypercalcemia is a higher-than-normal level of calcium in the
blood. In myeloma patients, hypercalcemia is the most frequent metabolic
complication of the disease, and it is more common with later diagnosis
of myeloma and with extensive bone involvement. Hypercalcemia usually
results from bone breakdown, which releases calcium from the bone into
the bloodstream.
Hypercalcemia can result in a number of symptoms, including loss of
appetite, nausea, thirst, fatigue, muscle weakness, restlessness, and
confusion. In patients with hypercalcemia due to myeloma, there is often

12 1.818.487.7455 • 1.800.452.CURE
impaired renal (kidney) function, and hypercalcemia complicates recovery
from kidney injury.
Renal (kidney) dysfunction
Impairment of kidney function is a common complication in patients with
myeloma. However, not every patient will have this problem. In some
patients, M-proteins (especially Bence-Jones proteins) cause renal injury by
a variety of mechanisms, ranging from tubular damage (resulting from large
accumulations of precipitated light chains) to selective tubular damage
(resulting in the metabolic effects of Fanconi syndrome), and to M-proteins
deposited as amyloid.
Other important factors related to kidney dysfunction in patients include
increased levels of calcium or uric acid, infection, and the effects of drugs
such as nephrotoxic antibiotics, nonsteroidal anti-inflammatory drugs
(NSAIDs), or contrast agents or dyes used for imaging studies. Gadolinium-
based contrast agents used with MRI have a potentially toxic effect, and
patients with kidney problems should first discuss their use with their doctor.
Awareness of potential kidney damage and maintenance of sufficient fluid
intake are especially important for patients with myeloma to help avert the
damaging effects of these various factors.
Anemia
Anemia is a characteristic feature of myeloma. Red blood cells (RBC)
contain hemoglobin, a protein that carries oxygen to the body’s tissues and
organs. Anemia is usually defined as a decrease in hemoglobin < 10 g/dL
or as a decrease of ≥ 2 g/dL from the normal level for an individual. More
than 13–14 g/dL is considered normal. Low levels of oxygen in the body
may cause shortness of breath and feelings of exhaustion. Many newly
diagnosed myeloma patients have anemia.
Although physical displacement of bone marrow RBC precursors is a
factor, the specific inhibition of RBC production by micro-environmental
cytokines and adhesion molecules is a more functional explanation.
Improvement in anemia occurs with successful treatment of the myeloma.
Recombinant epoietin alpha should be used with caution, as reports
have noted the association of epoietin with increased tumor growth and
reduced survival in cancer patients, and the identification of epoietin
receptors on myeloma cells.
Bone disease
Ever since the first recognition of myeloma in 1844, there has been
awareness of its unique type of bone disease. It has taken until quite
recently to determine the mechanisms involved. The first clue was that

myeloma.org 13
 both myeloma cells and increased numbers of osteoclasts are present at
sites of bone destruction. Many details of the mechanisms of bone disease
in myeloma are now understood, including the following:
¡ Myeloma cells produce osteoclast-activating factors (OAFs) while
inhibiting osteoblasts. “Coupling” between osteoclast and osteoblast
function is responsible for normal bone remodeling and repair. An
important observation is that the cholesterol-lowering statin drugs can
enhance osteoblast activity and promote bone healing. Both Velcade®
(bortezomib) and Revlimid® (lenalidomide) have been shown to promote
bone healing in addition to exerting potent anti-myeloma activity.
¡ Cytokines (i.e., interleukin-1β, interleukin-6, tumor necrosis factor-α,
and tumor necrosis factor-β), chemokines such as MIP-α, and cell-cell
adhesion processes involving β3 integrin are all involved in producing
increased numbers and activity of osteoclasts.
¡ The identification of a substance called RANK ligand (RANKL) as a
critical mediator of osteoclast activation.
For more information, read the IMF’s publication Understanding Treatment
of Myeloma Bone Disease.
Other dysfunction
Myeloma cells can accumulate in bone marrow or in tissue and produce a
broad range of potential complications, including the following:
¡ I nfections
Key aspects of infections in myeloma patients are reduced immunity
(because of myeloma) and low white blood cell counts (because of
myeloma build-up in bone marrow and/or the impact of treatment).
Infection or suspected infection must be promptly reported to your
myeloma doctor, who can assess the need for immediate supportive
care, such as treatment with antibiotic or antiviral therapy.
The predisposition to infections is perhaps the single most characteristic
feature of myeloma besides bone disease. The mechanisms responsible
for infection susceptibility are not fully understood. The presence of
active myeloma in the bone marrow results in impairment of normal
immune function, including inhibition of normal antibody production
(reflected by hypogammaglobulinemia), impaired T cell (T lympho-
cyte) function, and activated yet aberrant monocyte (a type of white
blood cell found in the circulation) or macrophage (a type of white blood
cell found in tissues) function. Some studies indicate that a factor
issuing from the activated macrophages both enhances the activity
of the myeloma cells and inhibits normal immunoglobulin production
and T-cell function.

14 1.818.487.7455 • 1.800.452.CURE
 Both neutropenia and hypogammaglobulinemia increase the
likelihood of infections, and patients with myeloma are susceptible
to a broad range of opportunistic infections.
¡N
 eurologic effects
Myeloma patients are susceptible to viral infections of nerve tissue, most
particularly varicella zoster (“shingles”), herpes zoster (“cold sores”),
Epstein-Barr virus (mononucleosis), cytomegalovirus (which may result
in partial facial paralysis called Bell’s Palsy), or other complications.
In myeloma patients, nerve tissue is often affected either by the direct
antibody effects of M-proteins against nerves (e.g., myelin sheaths)
or by deposition of amyloid fibrils on nerves, thus impairing function.
These effects result in peripheral neuropathies that must be
distinguished from other causes of neuropathy (e.g., diabetes mellitus,
multiple sclerosis, Parkinson’s disease).

Table 4. Schema of pathophysiology

Skeletal findings
• Solitary or multiple osteolytic lesions • Diffuse osteoporosis (osteopenia)
Associated effects of bone destruction
• Elevated serum calcium • Hypercaliuria (calcium increase in urine)
• Bone fractures • Loss of height (vertebral collapse)
Extramedullary (extraskeletal) myeloma
Soft tissue involvement, mostly common in head/neck area (e.g., nasopharynx); also in liver, kidney,
and other soft tissue sites including skin
Peripheral blood
• Anemia • Thrombocytopenia • Circulating monoclonal B
• Abnormal clotting • Plasma cell leukemia lymphocytes (precursors of
• Leukopenia • Circulating plasma cells myeloma cells)
Plasma protein changes
• Hyperproteinemia (elevated protein) • Narrowed anion gap (low serum sodium)
• Hypervolemia (expanded volume) • Elevated serum β2-microglobulin
• Monoclonal immunoglobulins • Decreased serum albumin
(IgG, IgA, IgD, IgE, IgM or light chains only) • Elevated serum IL-6 and C-reactive protein (CRP)
Kidney abnormalities
• Proteinuria, casts without leukocytes • Uremia (kidney failure)
or erythrocytes • Amyloidosis or light chain deposition disease
• Tubular dysfunction with acidosis and renal dysfunction
(Fanconi syndrome)

myeloma.org 15
 Neurologic problems in myeloma depend on the location of affected
nerves. For example, spinal cord compression and meningitis are the
result of plasma cell tumor formation or infiltration, and carpal tunnel
syndrome usually results from deposition of Bence Jones proteins.
¡P
 lasmacytomas
Both in bone and in soft tissue, plasmacytomas can result in compression
or displacement of nerves, the spinal cord, or even brain tissue. These
pressure effects often represent a medical emergency that requires
immediate treatment with radiation therapy, neurosurgery, and/or
high-dose steroids or other medications.
¡H
 yperviscosity
Hyperviscosity resulting from high levels of M-protein can cause problems
such as bruising, nose bleeding, hazy vision, headaches, gastrointestinal
bleeding, sleepiness, and a variety of ischemic neurological symptoms
caused by reduced blood and oxygen supply to the nerve tissue.
Hyperviscosity occurs in less than 10% of patients with myeloma and in
about 50% of patients with Waldenström macroglobulinemia (WM).
Increased bleeding is often exacerbated by thrombocytopenia as well
as by binding of M-proteins to clotting factors or platelets.

Response or remission
Response or remission are interchangeable terms to describe the complete
or partial disappearance of the signs and symptoms of myeloma. Remission
is generally considered to be at least a partial response (PR, ≥ 50% improve­
ment) which lasts for at least 6 months. These are the terms used to classify
the depth of response to treatment:
¡S
 tringent complete response (sCR)
sCR is CR (as defined below) plus normal FLC ratio and absence of clonal
cells in bone marrow by immunohistochemistry or immunofluorescence.
¡C
 omplete response (CR)
For myeloma, CR is negative immunofixation on serum (blood) and
urine, and disappearance of any soft tissue plasmacytomas, and
≤ 5% plasma cells in bone marrow. CR is not the same as a cure.
¡V
 ery good partial response (VGPR)
VGPR is less than CR. VGPR is serum M-protein and urine M-protein
detectable by immunofixation but not on electrophoresis, or 90% or
greater reduction in serum M-protein, plus urine M-protein less than
100 mg per 24 hours.
¡P
 artial response (PR)
PR is a level of response in which there is at least a 50% reduction in
M-protein, and reduction in 24-hour urinary M-protein by at least 90%
(or to less than 200 mg per 24 hours).

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 Table 5. Clinical trial phases

I Early testing to assess dosing, tolerance, and toxicity in patients

II Further testing to evaluate how effective treatment is at the dose and schedule selected

Comparison of the new treatment with prior treatment(s) to determine if the new
III
treatment is superior

Usually carried out after FDA approval to assess cost-effectiveness, quality of life impact,
IV
and other comparative issues

As treatment has improved, it has become more important to assess response

to treatment as accurately as possible. Besides the depth of response, one
must now consider even deeper responses as well as duration of response.
With the increasing efficacy of new combination therapies, response is now
assessed in terms of minimal residual disease (MRD) and MRD-negative
status. Concepts that were previously unattainable and unmeasurable in
myeloma, MRD levels are now verifiable with bone marrow testing. If or
when approved by the FDA, MRD testing will become the new clinical trial
endpoint, the standard means to measure depth of response in US-based
myeloma clinical trials.
Improvements in M-protein must be associated with evidence of clinical
improvement, such as reduced bone pain or improved RBC counts. It is
important to keep in mind that a higher percent regression in disease does
not automatically confer longer survival. When there is residual disease,
the characteristics of the remaining drug-resistant myeloma cells deter-
mine the outcome. These remaining myeloma cells may or may not have
a tendency for immediate regrowth. If there is no regrowth, this is called
“plateau phase” or “residual but stable disease.”
The fraction of resistant myeloma cells is primarily dependent upon
the intrinsic molecular features of the individual myeloma and the pre-
treatment tumor burden or stage. Responding patients go from a high-risk
status to a lower-risk status until, ideally, no signs of myeloma are left, or
they reach a stable plateau phase, but with measurable residual disease.
The time required to reach the plateau phase is variable, ranging from
rapid response in 3 to 6 months, to slow response in 12 to 18 months.
Important terms in assessing response are:
¡T
 ime-to-progression (TTP)
The time from start of treatment until relapse occurs.
¡P
 rogression-free survival (PFS)
The length of time during and after the treatment of myeloma that
a patient lives with the disease but the myeloma does not get worse.

myeloma.org 17
 In a clinical trial, PFS is one way to measure how well the treatment
is working.
¡P
 FS1 – The time from the start of therapy to the occurrence
of first relapse.
¡P
 FS2 – The time from start of therapy to the occurrence of
second relapse, incorporating the duration of both first and
second remissions.
¡P
 rogressive disease
Myeloma that is becoming worse or relapsing, as documented by tests.
Defined as an increase of ≥ 25% from the lowest confirmed response
value in the myeloma protein level and/or new evidence of disease.
For additional information, read the IMF’s Understanding Your Test Results
booklet that explains the tests used to monitor and assess myeloma
status throughout the disease course, and which tests are used to detect
response and relapse.

Relapsing or refractory myeloma

Relapsing disease
Relapse is the reappearance of signs and symptoms of myeloma after a
period of improvement. Patients with relapsed disease have been treated,
then developed signs and symptoms of myeloma at least 60 days after
treatment ended. In myeloma, it is not uncommon to experience a relapse
of disease following a remission. In fact, there can be multiple periods
of response and remission following treatment with consecutive lines of
therapy. Fortunately, a growing number of effective protocols are FDA-­
approved for relapsing disease, a significantly broader range of treatment
options than in years past.

Table 6. Prognostic factors

TEST SIGNIFICANCE

Serum β2 microglobulin (S β2M) The higher the level, the more advanced the stage.

Serum albumin (S ALB) The lower the level, the more advanced the stage.

C-reactive protein (CRP) Increased with active disease.

Serum lactate dehydrogenase (LDH) Increased with active disease.

Abnormal chromosomes on bone marrow Several chromosome deletions or translocations are

cytogenetics and fluorescence in situ considered high-risk; can be associated with shorter
hybridization (FISH) duration of remission.

18 1.818.487.7455 • 1.800.452.CURE
The aim of treatment at each relapse is to achieve optimal response with
the least toxicity. This is what leads to the best long-term outcome possible
for each patient with myeloma. Therapy for relapsed disease should be
based on underlying disease biology and patient characteristics. If risk
factors were identified when the patient was newly diagnosed and the
initial treatment choice was made, this knowledge will have an impact on
the choice of treatment when myeloma relapses. Additional risk factors
may also become evident at the time of relapse. Assessed individually and
taken together, these factors play a role in selecting treatment protocol for
refractory myeloma.
¡D
 uration and depth of initial therapy
Patients with myeloma experience their first relapse at variable
intervals after achieving their first remission. The duration and depth
of a patient’s response to initial therapy will help guide the selection
of the next course of treatment and is often predictive of long-term
efficacy in managing myeloma. Several phase III clinical trials have
demonstrated that patients who achieve MRD-negativity status have
a better PFS.

Table 7. IMWG criteria for response assessment including criteria for MRD
IMWG MRD criteria (requires a complete response as defined below)
Sustained MRD-negative
MRD (minimal residual disease) negativity in the marrow – NGF (next-generation flow), or NGS
(next-generation sequencing), or both – and by imaging as defined below, confirmed minimum
of 1 year apart. Subsequent evaluations can be used to further specify the duration of negativity
(eg, MRD-negative at 5 years)
Flow MRD-negative
Absence of phenotypically aberrant clonal plasma cells by NGF on bone marrow aspirates using
the EuroFlow standard operation procedure for MRD detection in multiple myeloma (or validated
equivalent method) with a minimum sensitivity of 1 in 105 nucleated cells or higher
Sequencing MRD-negative
Absence of clonal plasma cells by NGS on bone marrow aspirate in which presence of a clone is
defined as less than two identical sequencing reads obtained after DNA sequencing of bone marrow
aspirates using the LymphoSIGHT platform (or validated equivalent method) with a minimum
sensitivity of 1 in 105 nucleated cells or higher
Imaging-positive MRD-negative
MRD negativity as defined by NGF or NGS plus disappearance of every area of increased tracer uptake
found at baseline or a preceding PET/CT or decrease to less mediastinal blood pool SUV (maximum
standardized uptake value) or decrease to less than that of surrounding normal tissue
(Table 7 continues on next page)

myeloma.org 19
 Table 7. IMWG criteria for response assessment including criteria for MRD
(continued from previous page)

Standard IMWG response criteria

Stringent complete response

Complete response as defined below plus normal FLC ratio and absence of clonal cells in bone
marrow biopsy by immunohistochemistry (κ/λ ratio ≤ 4:1 or ≥ 1:2 for κ and λ patients, respectively,
after counting ≥ 100 plasma cells)

Complete response

Negative immunofixation on the serum and urine and disappearance of any soft tissue
plasmacytomas and < 5% plasma cells in bone marrow aspirates

Very good partial response

Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90%
reduction in serum M-protein plus urine M-protein level < 100 mg per 24 h

Partial response

• ≥ 50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by ≥ 90% or to

< 200 mg per 24 h;
• If the serum and urine M-protein are unmeasurable, a ≥ 50% decrease in the difference between
involved and uninvolved FLC levels is required in place of the M-protein criteria;
• If serum and urine M-protein are unmeasurable, and serum-free light assay is also unmeasurable,
≥ 50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow
plasma-cell percentage was ≥ 30%;
• In addition to these criteria, if present at baseline, a ≥50% reduction in the SPD (sum of
the products of the maximal perpendicular diameters of measured lesions) of soft tissue
plasmacytomas is also required

Minimal response

• ≥25% but ≤49% reduction of serum M-protein and reduction in 24-h urine M-protein by
50%–89%;
• In addition to the above listed criteria, if present at baseline, a ≥50% reduction in the size (SPD) of
soft tissue plasmacytomas is also required

Stable disease

Not recommended for use as an indicator of response; stability of disease is best described by
providing the time-to-progression estimates. Not meeting criteria for complete response, very good
partial response, partial response, minimal response, or progressive disease

(Table 7 continues on next page)

20 1.818.487.7455 • 1.800.452.CURE
 Table 7. IMWG criteria for response assessment including criteria for MRD
(continued from previous page)

Standard IMWG response criteria (continued)

Progressive disease
Increase of 25% from lowest confirmed response value in any one or more of the following criteria:
• Serum M-protein (absolute increase must be ≥ 0.5 g/dL);
• Serum M-protein increase ≥ 1 g/dL, if the lowest M component was ≥ 5 g/dL;
• Urine M-protein (absolute increase must be ≥ 200 mg/24 h);
• In patients without measurable serum and urine M-protein levels, the difference between involved
and uninvolved FLC levels (absolute increase must be >10 mg/dL);
• In patients without measurable serum and urine M-protein levels and without measurable involved
FLC levels, bone marrow plasma-cell percentage irrespective of baseline status (absolute increase
must be ≥ 10%);
• Appearance of a new lesion(s), ≥ 50% increase from nadir in SPD of > 1 lesion, or ≥ 50% increase in
the longest diameter of a previous lesion > 1 cm in short axis;
• ≥ 50% increase in circulating plasma cells (minimum of 200 cells per μL) if this is the only measure
of disease
Clinical relapse
Clinical relapse requires one or more of the following criteria:
• Direct indicators of increasing disease and/or end organ dysfunction (CRAB features) related to the
underlying clonal plasma-cell proliferative disorder. It is not used in calculation of time to progression
or progression-free survival but is listed as something that can be reported optionally or for use in
clinical practice;
• Development of new soft tissue plasmacytomas or bone lesions (osteoporotic fractures do not
constitute progression);
• Definite increase in the size of existing plasmacytomas or bone lesions. A definite increase is defined
as a 50% (and ≥ 1 cm) increase as measured serially by the SPD of the measurable lesion;
• Hypercalcemia (> 11 mg/dL);
• Decrease in hemoglobin of ≥ 2 g/dL not related to therapy or other non-myeloma-related conditions;
• Rise in serum creatinine by 2 mg/dL or more from the start of the therapy and attributable to myeloma;
• Hyperviscosity related to serum paraprotein
Relapse from complete response (to be used only if the end point is disease-free survival)
Any one or more of the following criteria:
• Reappearance of serum or urine M-protein by immunofixation or electrophoresis;
• Development of ≥ 5% plasma cells in the bone marrow;
• Appearance of any other sign of progression (ie, new plasmacytoma, lytic bone lesion, or
hypercalcemia see above)
Relapse from MRD negative (to be used only if the end point is disease-free survival)
Any one or more of the following criteria:
• Loss of MRD negative state (evidence of clonal plasma cells on NGF or NGS, or positive imaging study
for recurrence of myeloma);
• Reappearance of serum or urine M-protein by immunofixation or electrophoresis;
• Development of ≥ 5% clonal plasma cells in the bone marrow;
• Appearance of any other sign of progression (ie, new plasmacytoma, lytic bone lesion, or hypercalcemia)

myeloma.org 21
 ¡R
 e-utilizing the frontline regimen
If the first relapse occurs after a remission of at least 6 months, the
initial strategy for the management of relapsing disease is to consider
re-utilizing the patient’s frontline therapy that produced the remission
in the first place. NCCN guidelines for myeloma treatment state that
“if the relapse occurs greater than 6 months after completion of the
initial primary therapy, patients may be retreated with the same
primary regimen.”
Approximately 50% of patients will experience a second remission with
the same therapy that produced the first remission. This is particularly
true for patients whose disease is in remission for more than 1 year
following the initial treatment.
¡B
 iochemical relapse vs. clinical relapse
One factor to consider is the type of relapse. Is it biochemical or clinical?
Biochemical relapse means there is disease progression based on
increase in M-protein levels, but no myeloma-related symptoms of

Table 8. Tests required to monitor therapy responses

Blood tests
• Routine blood counts • Myeloma protein measurements (serum protein
• Chemistry panel electrophoresis plus quantitative immunoglobulins)
• Liver function tests • Serum free light chain assays (Freelite®)
• Serum β2 microglobulin • Heavy/light chain assay (Hevylite®)
• C-reactive protein • Peripheral blood labeling index (LI)
• Serum erythropoietin level
Urine
• Routine urinalysis
• 24-hour urine for measurement of total protein, electrophoresis, and immunoelectrophoresis
• 24-hour urine for creatinine clearance if serum creatinine elevated
Bone evaluation
• Skeletal survey by X-ray • Whole body FDG/PET scan if disease status unclear
• MRI/CT scan for special problems • Bone density measurement (DEXA scan) as baseline
and to assess benefit of bisphosphonates
Bone marrow
• Aspiration and biopsy for diagnosis and periodic monitoring
• Special testing to assess prognosis looking for multiple potential karyotypic and FISH abnormalities
(number of chromosomes, translocations, deletions – e.g., FISH 13q-, t[4;14], 1q21, etc.)
Other testing (special circumstances)
• Amyloidosis • Neuropathy • Renal or infectious complications

22 1.818.487.7455 • 1.800.452.CURE
 organ dysfunction. Still, a biochemical relapse may have a negative
impact on the patient’s quality of life. A biochemical relapse requires
monitoring of M-protein levels to catch disease progression if or
when it occurs. In high-risk myeloma, treatment should be initiated
early after biochemical relapse is diagnosed to avoid progression to
symptomatic disease. Treatment of biochemical relapse is indicated
if the following is detected:
¡ Doubling of serum M-protein,
¡ Increase of serum M-protein by 1 g/dL or more,
¡ Increase of urine M-protein by 500 mg per 24 hours or more,
¡ Increase of involved serum-free light chains (FLC) level
by 20 mg/dL or more,
¡ Abnormal ratio by 2 measurements taken 2 months apart.
Clinical relapse interventions vary depending upon the factors that
are present. For example, if there are new soft-tissue plasmacytomas
or bone lesions, your doctor may suggest radiation as a potentially
satisfactory way to manage the relapse. Treatment of clinical relapse
is indicated if the following is detected:
¡ Increase of 50% or more in size of existing plasmacytomas
or bone lesions,
¡ Hypercalcemia,
¡ Decrease in hemoglobin of 2 g/dL or more (due to myeloma),
¡ Increase in serum creatinine by 2 mg/dL or more (due to myeloma),
¡ Hyperviscosity requiring intervention.
¡R
 elapse with renal damage
Relapse in myeloma patients with renal damage, whether pre-existing
or newly identified, requires careful consideration of which protocol
may be most appropriate. There are several effective treatments that
can be used safely, including immunomodulatory agents, proteasome
inhibitors, and anti-CD38 monoclonal antibodies. In fact, data from
a subgroup of patients in the ICARIA-MM clinical trial demonstrate
that complete renal response can be achieved with a combination of
an anti-CD38 monoclonal antibody and a proteasome inhibitor. Other
clinical trials have demonstrated similar findings but with smaller
groups of patients.
¡R
 elapse with extramedullary disease
Relapse in patients with extramedullary myeloma is addressed
following the same principles as the management of high-risk disease
with chromo­somal abnormalities. Limited data is available on relapse
with extramedullary disease as few clinical trials include such patients.

myeloma.org 23
 Figure 8. Karyotype analysis of human chromosomes

Figure 9. Fluorescence in situ hybridization (FISH) of a myeloma cell

Figure 10. Chromosomal abnormalities in high-risk myeloma

Deletion Translocation

24 1.818.487.7455 • 1.800.452.CURE
 However, treatment with immunomodulatory agents and proteasome
inhibitors has demonstrated efficacy. Local radiation for local disease
control and pain relief, as well as surgical intervention should be
considered. PET/CT imaging is key to evaluating and monitoring
extramedullary myeloma.
¡R
 elapse after a transplant
In many cases of myeloma, relapse following a transplant has a pattern
similar to relapse following non-transplant treatment approaches.
A patient who had a durable remission of at least 2 years after a first
transplant should discuss with their doctor if having a second transplant
at relapse is a recommended strategery for achieving the next remission.
¡S
 equence of treatment regimens
The sequencing of treatment regimens for a relapsing patient is viewed
primarily based on the drugs to which the patient has become refractory.

Standard-of-care (SOC) regimens currently used for relapsed myeloma

include the following:
1. DPd – Darzalex® (daratumumab) + Pomalyst® (pomalidomide) +
dexamethasone,
2. DVd – Darzalex + Velcade® (bortezomib) + dexamethasone,
3. IRd – Ninlaro® (ixazomib) + Revlimid® (lenalidomide) + dexamethasone,
4. Kd – K
 yprolis® (carfilzomib) + dexamethasone,
5. EPd – Empliciti® (elotuzumab) + Pomalyst + dexamethasone.

Relapse is a key time to revisit the discussion you likely had with your
doctor at the time of your diagnosis about the overall strategy that is most
appropriate for you and your myeloma. This is also a key time to seek a
consultation with a myeloma specialist.

Refractory disease
Myeloma is considered to be refractory in patients who have had progressive
disease either during treatment or within 60 days following treatment.
Patients who have short remissions tend to have poor outcomes and are
considered to have high-risk myeloma.

Unfortunately, a subset of patients with myeloma may develop refractory

disease that is no longer responsive to standard treatments. However,
myeloma that is refractory to one agent in a drug class may be responsive to
another agent in the same drug class or to an agent from a different class. The
efficacy of a treatment protocol is dependent on the patient’s prior exposure
to a specific myeloma drug, as well as to other drugs in the same class.

myeloma.org 25
 Patients with refractory myeloma must select from a narrower range of
FDA-approved effective therapy options. The number of regimens a patient
has been exposed to and the length of time for a regimen to lose efficacy are
predictive of the outcome of therapy. The development of drug resistance
may emerge over time. Patients who are refractory to their initial therapy
tend to have poor outcomes and are considered to have high-risk myeloma.
In patients with chromosomal abnormalities or mutations, myeloma is more
likely to relapse quickly after treatment or to be refractory to treatment.
High-risk myeloma is defined by the chromosomal abnormalities t(4;14),
t(14;16), t(14;20), del 17p, and 1q gain, along with Revised International
Staging System (R-ISS) Stage III disease, and/or a high-risk gene expression
profile (GEP) signature. If this describes your myeloma, ask your doctor
which specific drugs and combinations have demonstrated the most
efficacy. Currently, there is no standard protocol for this group of patients,
and clinical trials are ongoing.
Given the use of combination therapies, it may be challenging to identify
which agent in a “triplet” (3-drug) or “quadruplet” (4-drug) protocol the
patient is refractory to, or to find effective protocol for patients who have

Table 9. Treatment goals and timely decision-making

TYPE OF TREATMENT Stabilizing Palliative
OBJECTIVE Countering the life-threatening Relieving discomfort and increasing
disruptions to body chemistry and the patient’s ability to function
the immune system
EXAMPLES • Plasmapheresis to thin the blood • Radiation to stop bone destruction
and avoid stroke • Red cell transfusion to relieve anemia
• Hemodialysis when kidney • Orthopedic surgery to repair and/or
function is impaired strengthen bone
• Drugs to reduce hypercalcemia
(may include chemotherapy)
TIME TO DECIDE Hours to Days Days to Months
TYPE OF TREATMENT Remission-Inducing Curative
OBJECTIVE Improving symptoms, slowing or Permanent remission*
arresting the course of the disease
EXAMPLES • Therapy to kill malignant cells • Stem cell transplants as a means of
throughout the body delivering high-dose chemotherapy
• Radiation to kill malignant cells
at a tumor site
TIME TO DECIDE Weeks to Months Weeks to Months
*Cure means permanent eradication of disease. “Functional cure” is a term that has been used to describe an
excellent response to treatment, when the patient is stable and in remission for many years from diagnosis,
but the myeloma is not completely eradicated.

26 1.818.487.7455 • 1.800.452.CURE
already received at least 2 prior lines of therapy as they may have already
used all the FDA-approved agents during their initial line of therapy and
at their first relapse. It is difficult to combine more than 4 drugs at a time
due to issues of toxicity. This may be a time to discuss with your doctor the
possible benefits of clinical trial participation.
Research indicates that immunotherapy treatments that enhance the
body’s natural defenses to fight cancer are the new wave of progress in
treatment approaches for myeloma. Monoclonal antibodies, bispecific
antibodies, antibody-drug conjugates (ADC), and chimeric antigen
receptor (CAR) T-cell therapies have demonstrated improved outcomes in
patients with refractory myeloma.
In late-stage relapse and with refractory disease, attaining stable disease
can have clinical benefits for the patient.

Drugs in use for myeloma

Various combination regimens have been used to treat myeloma since
melphalan, an alkylating agent, was first introduced in 1962. In the 1980s and
1990s, high-dose therapy (HDT) with melphalan followed by stem cell rescue
was one of the few techniques available to reduce a patient’s myeloma
tumor burden and achieve better outcomes. Melphalan continues to be
the conditioning regimen of choice for autologous stem cell transplants.
Thalidomide, an oral immunomodulatory agent that has been studied
since at least the 1950s, was first used to treat myeloma in a 1997 clinical
trial, ushering in the age of “novel therapies” in myeloma. In 2006,
thalidomide was approved by the FDA for patients with newly diagnosed
myeloma. Although thalidomide is now infrequently used in the U.S., many
myeloma patients around the globe have benefited from this therapy.
Thalidomide also gave rise to a next generation of immunomodulatory
agents with increased efficacy and reduced side effects, the drugs
Revlimid® (lenalidomide) and Pomalyst® (pomalidomide).
Below is a list of drugs approved for use in myeloma by the FDA in the era
of novel agents. The list is current as of the printing of this booklet and is
organized alphabetically.
1. Abecma® (idecabtagene vicleucel or “ide-cel”) is a first-in-class
B-cell maturation antigen (BCMA)-directed CAR T-cell immuno­
therapy approved by the FDA (March 2021) for relapsed or refractory
myeloma after 4 or more prior lines of therapy. Abecma is being
studied in earlier disease settings. Abecma is a personalized immuno­
therapy delivered as a one-time infusion of the patient’s own T cells
that have been “harvested” from the bloodstream and engineered to
identify and destroy the myeloma cells.

myeloma.org 27
 2. Aredia® (pamidronate) is a bisphosphonate approved by the FDA
(September 1998) to treat myeloma bone disease and that of other
types of cancer.
3. Carvykti® (ciltacabtagene autoleucel or “cilta-cel”) is the
second BCMA-directed CAR T-cell therapy approved by the FDA
(February 2022) for relapsed or refractory myeloma after 4 or more
prior lines of therapy. Data from clinical trials in earlier disease
settings demonstrate impressive results at first relapse. Carvykti is
manufactured for each individual patient using the patient’s own
T cells, then delivered as a one-time infusion.
4. Darzalex® (daratumumab) is the first-in-class monoclonal antibody
that targets the CD38 protein on the surface of myeloma cells. It was
approved by the FDA (November 2015) as an intravenous (IV) infusion.
Darzalex Faspro® (daratumumab and hyaluronidase-fihj) is a newer
formulation approved by the FDA (May 2020) as a subcutaneous (SQ)
injection under the skin. Either formulation of Darzalex can be used
for newly diagnosed myeloma and throughout the disease course.
5. Dexamethasone is a generic steroid also known by several brand
names. It is one of the most frequent medications used in myeloma
combination therapies.
6. Empliciti® (elotuzumab) is the first immunostimulatory monoclonal
antibody approved by the FDA (November 2015) for the treatment of
myeloma after 1 to 3 prior therapies.
7. Kyprolis® (carfilzomib) is the second proteasome inhibitor approved
for myeloma by the FDA (July 2012). Kyprolis was originally approved for
the treatment of myeloma after at least 2 prior therapies; now it can
be used at first relapse. It is given by intravenous (IV) infusion.
8. Ninlaro® (ixazomib) is the third proteasome inhibitor approved by
the FDA (November 2015) and it is the first proteasome inhibitor
that is taken orally (by mouth). Ninlaro can be used for relapsed or
refractory myeloma after at least 1 prior therapy.
9. Pomalyst® (pomalidomide) is the third immunomodulatory agent
approved by the FDA (February 2013) for use in myeloma. It is taken
orally and can be used for relapsed or refractory myeloma after at
least 2 prior therapies.
10. Revlimid® (lenalidomide) is an immunomodulatory agent, the first
oral medication for myeloma approved by the FDA (June 2006).
Revlimid was originally approved for use in patients who had
received at least 1 prior therapy. In February 2015, the FDA expanded
this indication to a broad approval for use throughout the myeloma
disease course, from diagnosis through relapse. In February 2017,

28 1.818.487.7455 • 1.800.452.CURE
 Revlimid was approved as maintenance therapy after ASCT. Revlimid
is part of standard of care (SOC) regimens.
11. Sarclisa® (isatuximab-irfc) is an anti-CD38 monoclonal antibody
approved by the FDA (March 2020) for patients with relapsed or
refractory myeloma who have received at least 1 prior therapy.
Sarclisa is given as an IV infusion.
12. Tecvayli™ (teclistamab-cqyv) is a first-in-class bispecific BCMA-
directed CD3 T-cell engager approved by the FDA (October 2022).
This “off-the-shelf” immunotherapy is delivered by injection.
13. Velcade® (bortezomib) is the first-in class proteasome inhibitor
approved by the FDA (May 2003). Velcade is available for administration
by IV infusion or SQ shot under the skin. Velcade is used throughout
the myeloma disease course, from diagnosis through relapse, and is
part of SOC regimens.
14. Xgeva® (denosumab) is a RANK ligand inhibitor approved by the FDA
(January 2018) for the prevention of skeletal-related events in patients
with myeloma.
15. Xpovio® (selinexor) is a first-in-class selective inhibitor of nuclear
export (SINE) compound approved by the FDA (July 2019) for the
treatment of patients with relapsed or refractory myeloma who
have received at least 4 prior therapies. In December 2020, the FDA
approved the use of Xpovio after at least 1 prior therapy. Xpovio is
taken in tablet form.
16. Zometa® (zoledronic acid) is a bisphosphonate approved by the
FDA (February 2002) to treat myeloma bone disease and that of other
types of cancer.
A myeloma patient must have a careful and detailed discussion with their
doctor about treatment choices that are most appropriate for them. Open
dialogue to discuss the pros and cons of each option is crucial. The addition
of many new agents to the myeloma armamentarium has presented doctors
with the challenge of determining the best combinations as well as the
optimal sequencing of treatment for each patient.
What has become clear is that no single therapy is likely to be effective
for every myeloma patient, nor is any single agent likely to achieve a cure
on its own. Rather, the combination approach that attacks myeloma cells
with multiple drugs through multiple pathways has thus far demonstrated
superior efficacy.
There is no simple answer to the question of “the best” treatment options
available today. Fortunately, there are numerous regimens that can produce
very deep and durable responses, with remissions lasting 2 or more years,

myeloma.org 29
 and improved overall survival (OS). The best choice for each patient depends
upon individual factors, including age, stage of myeloma, genetic features,
kidney status, comorbidities, cost, and of course, personal preference.
Radiation therapy
Local radiation can be dramatically effective. This is an important modality
of treatment for myeloma patients with severe local problems, such as
bone destruction, pain, and/or pressure on nerves or the spinal cord. The
major disadvantage, however, is that radiation therapy permanently dam-
ages normal bone marrow stem cells in the area of treatment. Wide-field
radiation encompassing large amounts of normal bone marrow should
be avoided. A general strategy is to rely on systemic treatment to achieve
overall disease control, limiting the use of local radiation therapy to areas
with particular problems.

Clinical trials
Myeloma researchers around the world are working to improve patient
survival as well as their quality of life. There is tangible progress in the
search for a cure, and we are getting closer to a functional cure, a term
used to describe a patient in a prolonged remission, with a small amount of
myeloma still detectable but not causing relapse or disease progression.
The rapid rate of development of new therapies for myeloma, as well as
investigation of new combinations of existing and emerging agents, can
make clinical trials an appropriate option for patients with relapsed or
refractory myeloma. Some clinical trials may be a potentially beneficial
option for patients in late relapse. Other clinical trials may be a good fit for
patients who experience early relapse after 1 or 2 lines of therapy.
To learn more about clinical trials and to determine if enrollment in a study
is the right decision for you, we encourage you to discuss your specific
options with the doctor treating your myeloma and to read the IMF’s
publication Understanding Clinical Trials.

Supportive care
A full range of supportive care measures is crucial for the management of
the disease and to alleviate the physical and emotional impact of living
with myeloma. The following IMF publications may be helpful:
¡U nderstanding Treatment of Myeloma Bone Disease
¡U nderstanding Fatigue
¡U nderstanding Peripheral Neuropathy in Myeloma
¡U nderstanding Treatment of Myeloma-Induced
Vertebral Compression Fractures

30 1.818.487.7455 • 1.800.452.CURE
Beyond the management of specific symptoms, other supportive measures
are also important:
¡A
 ntibiotics and antivirals
Infections are a common and recurrent problem in patients
with myeloma, and having a strategy for infection management
is essential. Ask your doctor about antibiotic therapy if active
infection is suspected, and if prophylactic antiviral therapy and/or
the Shingrix® vaccine should be considered in your case. For the
latest updates and information for myeloma patients about the
COVID-19 virus, vaccines, boosters, treatments, and more, please
visit myeloma.org/covid19-myeloma-patients.
¡P
 hysical activity
Check with your doctor to clarify if full physical activity is feasible or
if adjustments must be made due to bone disease or bone damage.
Usually, some physical activity can be planned, such as walking or
swimming, flexibility and strength exercises, and/or a personalized
yoga program.
¡D
 iet
No specific diet has been developed for myeloma patients, although
research has clearly demonstrated the link between obesity and
myeloma. We recommend a healthy, Mediterranean diet emphasizing
fruits, vegetables, fish, other lean animal proteins, whole grains, and
unprocessed “real” foods. Avoid foods that include processed sugars
and artificial trans fats. Caution should be used in two areas:
¡H
 erbal and vitamin supplements – Check with your doctor
or pharmacist before taking supplements while receiving
treatment for myeloma. Some interactions between drugs and/or
supplements can prevent myeloma treatments from working
effectively and some interactions can create serious medical
problems. Pharmacies have reference resources to help identify
potential interactions.
¡V
 itamin C – Doses greater than 1000 mg per day may be counter­
productive in myeloma and can increase the risk of kidney damage.
¡M
 ental health
Your mental health is critical as you move forward with planned
treatment. Make sure you’re comfortable with the treatment plan.
Schedule an appointment with a mental health professional if you
believe that you might be anxious or depressed or if others are
concerned that you might be depressed. This is a normal response to
a cancer and most cancer patients will need some help at one time

myeloma.org 31
 or another. Support among peers is vital at this time, and a myeloma
support group can be helpful in this context. For a referral to a
myeloma support group, visit support.myeloma.org and contact
the IMF InfoLine at 1.818.487.7455 or InfoLine@myeloma.org.
¡R
 egular sleep
This is very important for your immune system.
¡M
 ake adjustments
If possible, reduce stress in job, family, or social situations, and avoid
crowds and close contact with school-age children. Wash your hands
frequently. Your immune system is compromised both by the disease
and the treatments. Management of your myeloma is the top priority
until remission, or until a stable situation has been reached.

In closing
This booklet is not meant to replace the advice of your doctors and nurses
who are best able to answer questions about your specific healthcare
management plan. The IMF intends only to provide you with information
that will guide you in discussions with your healthcare team. To help
ensure effective treatment with good quality of life, you must play an
active role in your own medical care.
We encourage you to visit myeloma.org for more information about
myeloma and to contact the IMF InfoLine with your myeloma-related
questions and concerns. The IMF InfoLine consistently provides the most
up-to-date and accurate information about myeloma in a caring and
compassionate manner. Contact the IMF InfoLine at 1.818.487.7455
or InfoLine@myeloma.org.

Terms and definitions

The following selected terms are used in this booklet, while a more
complete compendium of myeloma-related vocabulary can be found
in the IMF’s Glossary of Myeloma Terms and Definitions located
at glossary.myeloma.org.
Anemia: Red blood cells contain hemoglobin, a protein that carries oxygen
to the body’s tissues and organs. Anemia is usually defined as a decrease
in hemoglobin < 10 g/dL or as a decrease of ≥ 2 g/dL from the normal
level for an individual. More than 13–14 g/dL is considered normal. Low
levels of oxygen in the body may cause shortness of breath and feelings
of exhaustion. Many newly diagnosed myeloma patients have anemia.
Antibody: A protein produced by plasma cells in response to an antigen
that enters the body. See “Immunoglobulin (Ig).”

32 1.818.487.7455 • 1.800.452.CURE
Antibody-drug conjugate (ADC): An anti-cancer therapy that links a
monoclonal antibody directed at cancer cells with a drug that is toxic to
cancer cells.
Antigen: Any foreign substance that causes the immune system to
produce natural antibodies. Examples of antigens include bacteria, viruses,
parasites, fungi, and toxins.
B-cell maturation antigen (BCMA): A protein involved in myeloma cell
growth and survival. BCMA is found on the surface of cells in all patients
with myeloma. Also called “tumor necrosis factor receptor superfamily
member 17 (TNFRSF17).”
Bence-Jones myeloma: Myeloma characterized by the presence of
Bence-Jones protein, an abnormal protein in urine made up of free kappa
or lambda light chains. See “Bence-Jones protein.”
Bence-Jones protein: A myeloma monoclonal protein. The protein is
composed of either free kappa or free lambda light chains. Because of their
small size, Bence-Jones light chains can be filtered through the kidneys
and pass into the urine. The amount of Bence-Jones protein in the urine is
expressed in terms of grams per 24 hours. Normally, a very small amount
of protein (< 0.1 g/24 h) can be present in the urine, but this is albumin
rather than Bence-Jones protein. The presence of any Bence-Jones protein
in the urine is abnormal. Myeloma protein heavy chains are too large to be
filtered through the kidneys. See “Bence-Jones myeloma.”
Biopsy: The removal of a sample of tissue for microscopic examination to
aid in diagnosis.
Bispecific antibody: An artificial antibody that binds to two (“bi”)
targeted cells.
Bisphosphonate: A type of drug that protects against osteoclast activity
(bone breakdown) and binds to the surface of bone where it is being
resorbed or destroyed.
Bone marrow: The soft, spongy tissue in the center of bones that produces
white blood cells, red blood cells, and platelets. When myeloma is growing,
myeloma cells build up in the bone marrow.
Bone marrow aspiration: The removal, by a needle, of a sample of fluid
and cells from the bone marrow for examination under a microscope.
Calcium: A mineral found mainly in the hard part of bone matrix
(hydroxyapatite). If produced or released in excess, it can build up in the
bloodstream. See “Hypercalcemia.”

myeloma.org 33
 Cancer: A term for diseases in which malignant cells divide without
control. Cancer cells can invade nearby tissues and spread through the
bloodstream and lymphatic system to other parts of the body.
Chemokine: A type of secreted protein within the cytokine family whose
function is to induce cell migration. See “Cytokine.”
Chimeric antigen receptor (CAR) T-cell therapy: In myeloma, this
immunotherapy involves collecting the patient’s T cells, and engineering
them to attack the patient’s own cancer cells.
Chromosome: A strand of DNA and proteins in the nucleus of a cell.
Chromosomes contain genes and function in the transmission of genetic
information. Normally, human cells contain 46 chromosomes (23 pairs).
•C
 hromosomal deletion – Genetic mutation in which part or all of a
chromosome is lost during DNA replication. Chromosomal deletions that
occur in myeloma include loss of the long arm of chromosome 13 (written
as 13q-) or loss of the short arm of chromosome 17 (written as 17p-).
•C
 hromosomal translocation – Genetic mutation in which parts of
different chromosomes are rearranged. Written with a lowercase
“t” followed by the numbers of the chromosomes with translocated
genetic material. Translocations that occur in myeloma include t(4;14),
t(11;14), t(14;16), and t(14;20).
Conditioning regimen: A treatment given to a patient to destroy cancer
cells prior to stem cell transplant. The most common conditioning regimen
given to myeloma patients is 200 mg of melphalan per square meter of
body mass.
Cytokine: A cytokine is a protein that circulates in the bloodstream, usually
in response to infection. Cytokines can stimulate or inhibit the growth or
activity in other cells.
Electrophoresis: A laboratory test used both for diagnosis and for
monitoring, in which a patient’s serum (blood) or urine proteins are
subjected to separation according to their size and electrical charge. Serum
or urine electrophoresis (SPEP or UPEP) enables both the calculation of the
amount of myeloma protein and the identification of the type of M-spike
for each patient.
Extramedullary plasmacytoma: A tumor of monoclonal plasma cells that
is found in soft tissue outside of the bone marrow and separate from bone.
Fanconi syndrome: A type of selective kidney tubular damage that affects
how kidneys reabsorb certain essential substances. Leakage of amino acids

34 1.818.487.7455 • 1.800.452.CURE
and phosphates into the urine, then exiting your body in the urine, can
cause metabolic bone disease.
Free light chain (FLC): An immunoglobulin light chain is the smaller of
two units that make up an antibody. There are two types of light chain:
kappa and lambda. A light chain may be bound to a heavy chain or it may
be unbound (free). Free light chains circulate in the blood and are small
enough to pass into the kidneys, where they may be filtered out into the
urine or may stick together and block the kidney’s tubules.
Heavy chain: An immunoglobulin protein produced by plasma cells is
made up of 2 heavy chains and 2 light chains, with the heavy chains being
the larger of the two units. The five types of heavy chains are based on the
class (isotype) of immunoglobulin produced by the myeloma cell (G, A, D,
E, or M). See “Immunoglobulin (Ig).”
Hypercalcemia: A higher than normal level of calcium in the blood. In
myeloma patients, it usually results from bone breakdown with release
of calcium from the bone into the bloodstream. This condition can cause
a number of symptoms, including loss of appetite, nausea, thirst, fatigue,
muscle weakness, restlessness, and confusion. See “Calcium.”
Hyperviscosity syndrome (HVS): When blood becomes so thick that the
reduced blood flow in smaller vessels causes complications, which can be
life-threatening. Treatment and management include intravenous fluids
and plasmapheresis.
Hypogammaglobulinemia: A laboratory diagnosis made when the
immune system is not producing enough immunoglobulin G (IgG)
in the blood.
Immune system: The body’s defense system, which destroys infected and
malignant cells and removes cellular debris. The immune system includes
white blood cells and organs and tissues of the lymphatic system.
Immunoglobulin (Ig): A protein produced by plasma cells; an essential
part of the body’s immune system. Immunoglobulins attach to foreign
substances (antigens) and assist in destroying them. The classes (isotypes)
of immunoglobulins are IgG, IgA, IgD, IgE, and IgM. Each type of immuno­
globulin has a different function in the body. See “Antibody” and “Antigen.”
• I gG, IgA – The two most common types of myeloma. The G and A refer
to the immunoglobulin heavy chain produced by the myeloma cells.
• IgD, IgE – These types of myeloma occur less frequently.
• I gM – This is a rare type of myeloma. IgM myeloma is not the same
as Waldenström macroglobulinemia.

myeloma.org 35
 Interleukin: A naturally produced chemical released by the body, or a
substance used in biological therapy. Interleukins stimulate the growth
and activities of certain kinds of white blood cells. Interleukin-2 (IL-2) is a
type of biological response modifier that stimulates the growth of certain
blood cells in the immune system that can fight some types of cancer.
Interleukin-6 (IL-6) is a cytokine that is a potent stimulus to osteoclast and
plasma cell growth.
Lesion: An area of abnormal tissue; a lump or abscess that may be caused
by injury or disease, such as cancer. In myeloma, “lesion” can refer to a
plasmacytoma or a hole in the bone.
•D
 iffuse lesion – A spread-out pattern of myeloma bone marrow
involvement in an area of bone.
• F ocal lesion – A defined area of irregular cells seen in the bone marrow
on MRI and PET-CT studies. In order to be considered diagnostic of
myeloma, there must be at least 2 focal lesions seen on MRI that are
at least 5mm in size.
• L ytic lesion – The damaged area of a bone that appears as a dark spot
on an X-ray when at least 30% of the healthy bone in any one area is
eaten away. Lytic lesions look like holes in the bone and are evidence
that the bone is being weakened. See “Lytic (lysis).”
Light chain: An immunoglobulin light chain is the smaller of two units
of an antibody. The light chains are bound by chemical bonds to the
ends of the heavy chains, but we make extra light chains that enter the
bloodstream. These are called “free light chains.” There are two types of
light chains: kappa and lambda.
Lytic (lysis): Dissolution or destruction of cells or tissues.
M-spike: A monoclonal spike, the sharp pattern that occurs on protein
electrophoresis tests, is a marker for the activity of myeloma cells.
See “Monoclonal” and “Monoclonal protein.”
Metabolism: The conversion of one compound into another compound,
which occurs during a living organism’s life-sustaining chemical processes.
See ”Metabolite.”
Metabolite: Any substance that is formed during metabolism or that is
necessary for metabolism. See ”Metabolism.”
Minimal residual disease (MRD): The presence of residual tumor
cells after treatment has been completed and complete response (CR)
has been attained. Even patients who have attained a stringent CR (sCR)
may have MRD. Very sensitive new testing methods are able to detect

36 1.818.487.7455 • 1.800.452.CURE
1 myeloma cell among 1,000,000 sampled cells in blood or bone marrow.
See “MRD-negative.”
Molecule: The smallest particle that retains all the properties of the
substance. A molecule is an electrically neutral group composed of two or
more atoms held together by chemical bonds.
Monoclonal: A clone or duplicate. Myeloma cells are derived from a
monoclone, a single malignant plasma cell in the bone marrow. The type
of myeloma protein produced is also monoclonal, a single form rather than
many forms (polyclonal). The important practical aspect of a monoclonal
protein is that it shows up as a sharp spike M-spike on the protein
electrophoresis test. See “M-spike.”
Monoclonal antibody: An antibody manufactured in a lab rather than
produced in the human body. Monoclonal antibodies are specifically
designed to find and bind to cancer cells and/or immune system cells for
diagnostic or treatment purposes. Monoclonal antibodies can be used
alone, or they can be used to deliver drugs, toxins, or radioactive material
directly to tumor cells.
Monoclonal protein (myeloma protein, M-protein): An abnormal
protein produced by myeloma cells that accumulates in and damages bone
and bone marrow. It is found in unusually large amounts in the blood and/or
urine of myeloma patients. See “Monoclonal” and “M-spike.”
MRD-negative: Minimal residual disease-negative. Depending on the test,
not even one myeloma cell found in 100,000 or 1,000,000 sampled bone
marrow plasma cells. See “Minimal residual disease (MRD).”
Multiple myeloma: A cancer of the bone marrow plasma cells, white blood
cells that make antibodies. Cancerous plasma cells are called myeloma cells.
Neuropathy: A feeling of numbness, tingling, burning, and/or pain caused
by nerve damage. See “Peripheral neuropathy.”
Neutropenia: A reduced level of neutrophils, a type of white blood cell
necessary to combat bacterial infection. Having too few neutrophils can
lead to infection. Fever is the most common sign of neutropenia. If you
have a fever, you must get immediate medical attention.
Non-secretory myeloma: Approximately 1% of myeloma patients do not
have detectable M-protein in the blood (serum) and urine. Some of these
patients can be successfully monitored using the serum free light chain
assay; others may be monitored with bone marrow biopsy and/or PET-CT
scan. Patients with non-secretory myeloma are treated in the same fashion
as those with M-protein-secreting disease.

myeloma.org 37
 Osteoblast: A bone cell associated with production of bone tissue.
Osteoblasts produce osteoid, which then becomes mineralized with
calcium to form new hard bone.
Osteoclast: A cell found at the junction between the bone marrow and
the bone. It is responsible for breaking down or remodeling old bone
tissue. In myeloma, the osteoclasts are overstimulated, while osteoblast
activity is blocked. The combination of accelerated bone resorption and
blocked new bone formation results in lytic lesions.
Peripheral neuropathy (PN): Peripheral neuropathy is a serious condition
that affects nerves in the hands, feet, lower legs, and/or arms. Patients
may experience PN from the effects of the myeloma itself and/or from
treatments for myeloma. Symptoms may include a feeling of numbness,
tingling, burning, and/or pain.
Plasma cells: White blood cells that produce antibodies. Myeloma cells
are cancerous plasma cells, which produce monoclonal protein (myeloma
protein, M-protein) that can lead to organ and tissue damage (anemia,
kidney damage, bone disease, and nerve damage).
Plasmacytoma: See “Extramedullary plasmacytoma” and
“Solitary plasmacytoma of bone (SPB).”
Plasmapheresis: The process of removing certain proteins from the blood.
Plasmapheresis can be used to remove high levels of M-protein from the
blood of myeloma patients.
Platelets: One of the three major types of blood cells, the others being
red blood cells and white blood cells. Platelets plug up breaks in the blood
vessel walls and release substances that stimulate blood clot formation.
Platelets are the major defense against bleeding. Also called thrombocytes.
Proteasome: A joined group (“complex”) of enzymes (“proteases”) that
break down the damaged or unwanted proteins in both normal cells and
cancer cells into smaller components. Proteasomes also carry out the
regulated breakdown of undamaged proteins in the cell, a process that is
necessary for the control of many critical cellular functions. These smaller
protein components are then used to create new proteins required by
the cell. This is important for maintaining balance within the cell and for
regulating cell growth.
Proteasome inhibitor: Any drug that interferes with the normal function
of the proteasome. See “Proteasome.”

Radiation therapy: Treatment with X-rays, gamma rays, or electrons to

damage or kill malignant cells. Radiation may be delivered from outside
the body or from radioactive materials implanted directly in the tumor.

38 1.818.487.7455 • 1.800.452.CURE
Red blood cells (RBC): Also called erythrocytes, these cells in the
blood contain hemoglobin, deliver oxygen to all parts of the body, and
take away carbon dioxide. Red blood cell production is stimulated by a
hormone (erythropoietin) produced by the kidneys. Myeloma patients with
damaged kidneys don’t produce enough erythropoietin and can become
anemic. Myeloma patients can also become anemic because of myeloma
cells’ effect on the ability of bone marrow to make new red blood cells.
Relapse: The reappearance of signs and symptoms of myeloma after a
period of improvement. Patients with relapsed disease have been treated,
then developed signs and symptoms of myeloma at least 60 days after
treatment ended. Most clinical trials for advanced myeloma are for patients
with relapsed and/or refractory disease.
Selective inhibitor of nuclear export (SINE): Selective inhibitor of
nuclear export (SINE): A compound that prevents cells from expelling
tumor suppressor proteins, which help protect the cell from cancer. When
tumor suppressors accumulate in a myeloma cell, they can counteract
the pathways that allow cancer cells to grow and divide, which leads to
myeloma cell death. Also known as XPO1 inhibitors.
Solitary plasmacytoma of bone (SPB): A discrete, single mass of
monoclonal plasma cells in a bone. The diagnosis of SPB requires a
solitary bone lesion, a biopsy of which shows infiltration by plasma cells;
negative imaging results for other bone lesions; absence of clonal plasma
cells in a random sample of bone marrow; and no evidence of anemia,
hypercalcemia, or renal involvement suggesting systemic myeloma.
Steroid: A type of hormone. Steroidal hormones are produced by
the body. Synthetic analogues (equivalents) of some steroids can
be manufactured in a laboratory. Dexamethasone, prednisone, and
methylprednisolone are synthetic steroids that have multiple effects and
are used for a number of conditions, including myeloma.
Stem cells (hematopoietic stem cells): The immature cells from which all
blood cells develop. Normal stem cells give rise to normal blood compo-
nents, including red cells, white cells, and platelets. Stem cells are normally
located in the bone marrow and can be harvested for transplant.
T cell (T lymphocyte): A type of white blood cell that plays a central role in
the immune system. T cells can be distinguished from other lymphocytes,
such as B cells and natural killer (NK) cells, by the presence of a T-cell
receptor (TCR) on the cell surface. They are called T cells because they
mature in the thymus, although some also mature in the tonsils.
Thrombocytopenia: A low number of platelets in the blood. Platelets
help blood to clot; fewer platelets can lead to easier bruising, bleeding,

myeloma.org 39
 and slower healing. The “normal” level of platelets varies from laboratory
to laboratory. For example, at Mayo Clinic the “normal” level is 150,000 or
more platelets per microliter of circulating blood. Bleeding problems could
occur if the count is less than 50,000 platelets. Major bleeding is usually
associated with a reduction to less than 10,000 platelets.
Tumor: An abnormal mass of tissue that results from excessive cell division.
In myeloma, a tumor is referred to as a plasmacytoma.
Tumor necrosis factor (TNF): A cell signaling protein (cytokine) involved
in systemic inflammation and bone resorption. TNF alpha (TNF-α) is
elevated in myeloma patients.
Waldenström macroglobulinemia (WM): A rare type of non-Hodgkin’s
lymphoma (NHL) that affects plasma cells. Excessive amounts of IgM
protein are produced. WM is not a type of myeloma.
White blood cells (WBC): General term for a variety of leukocytes
responsible for fighting invading germs, infections, and allergy-causing
agents. These cells begin their development in bone marrow and then
travel to other parts of the body. Specific white blood cells include
neutrophils, basophils, eosinophils, lymphocytes, and monocytes.

40 1.818.487.7455 • 1.800.452.CURE
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42 1.818.487.7455 • 1.800.452.CURE
 Connect. Be Informed.
Take Charge.
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