i3 Health is pleased to make the Clinician's Resource Guide from this activity available for use as a nonaccredited self-study or teaching resource.

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Clinical Tools and Resources for
Self-Study and Patient Education
MULTIPLE MYELOMA
REFERENCE GUIDE
The clinical tools and resources contained herein are provided as educational adjuncts to the
CME/CE/CPE-approved visiting faculty series Evolving Treatment Paradigms in Multiple
Myeloma and Implications for Shared Decision Making.
CONTENTS
I. Multiple Myeloma: Initial Tests for Diagnosis............................................................... 2
A. Blood Chemistry Tests...................................................................................... 2
B. Serum Quantitative Immunoglobulin Tests ...................................................... 3
C. Imaging Tests ................................................................................................... 4
D. Additional Tests ............................................................................................... 5
II. Multiple Myeloma: Staging.......................................................................................... 8
III. Treatments for Multiple Myeloma............................................................................... 9
IV. Combination Therapies for Multiple Myeloma......................................................... 10
V. Multiple Myeloma: Stem Cell Transplant .................................................................. 11
VI. Multiple Myeloma: Supportive Care......................................................................... 12

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I. MULTIPLE MYELOMA: INITIAL TESTS FOR DIAGNOSIS
A. BLOOD CHEMISTRY TESTS
Test Explanation
BUN
• Waste product made by the liver that is filtered out of the blood into urine by
the kidneys
• High levels in the blood may be a sign of kidney damage
Creatinine
• Waste from muscles that is filtered out of the blood into urine by the kidneys
• High levels of creatinine in the blood may be a sign of kidney damage
• A creatinine clearance involves taking a 24-hour sample of urine and
comparing it to the level of creatinine in the blood. This test is needed to see
how well the kidneys are working
Electrolytes
• Minerals in the blood that are needed for organs to work well
• High levels of electrolytes such as sodium, potassium, and calcium may be a
sign of kidney damage
Calcium
• A mineral found in many body tissues, but mostly in the bones
• High levels of calcium in the blood may be a sign of myeloma destroying
bone
• Too much calcium in the blood can damage the kidneys
Albumin
• The main protein in blood plasma
• Low albumin levels may be a sign of advanced myeloma
LDH
• A protein made by many types of cells, including myeloma cells
• High LDH levels may be a sign of advanced myeloma
Beta-2 microglobulin
• A protein made by many types of cells, including myeloma cells
• High beta-2 microglobulin levels may be a sign of advanced myeloma
Uric acid
• One of the chemicals released by dying cancer cells
• Very high levels of uric acid and other chemicals in the blood can be very
dangerous, causing serious damage to organs such as the kidneys
National Comprehensive Cancer Network (2019). NCCN Guidelines for Patients®: multiple myeloma. Version 2.2019.
Available at: http://www.nccn.org/patients

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B. SERUM QUANTITATIVE IMMUNOGLOBULIN TESTS
Test Explanation
Serum free light chain assay
• Measures the amount of free light chains in the blood
• Helpful even when it is not possible to measure the amount of M-
proteins in the blood or urine using electrophoresis
SPEP
• Measures the amount of M-proteins in the blood
• High levels may be a sign of advanced myeloma
SIFE
• Identifies the type of M-proteins present in the blood by showing which
form of heavy chains and light chains are present
Serum viscosity
• Measures the thickness of the blood
• A large amount of M-proteins in the blood can cause blood to become
very thick (hyperviscosity)
• Hyperviscosity can cause neurologic symptoms, headaches, vision
problems, bleeding, and damage to kidneys and other organs
HLA typing
• A blood test that finds a person’s HLA type in order to find the right
donor for an allogeneic stem cell transplant
• HLAs are special proteins found on the surface of most cells in the body
that help the body to distinguish between its own cells and foreign cells
• HLAs affect how the body responds to foreign substances
National Comprehensive Cancer Network (2019). NCCN Guidelines for Patients®: multiple myeloma. Version 2.2019.
Available at: http://www.nccn.org/patients

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C. IMAGING TESTS
Surveys/Scans
Bone survey
• Uses a set of x-rays of the entire skeleton to check for broken or damaged bone
caused by myeloma
MRI scan
• Uses radio waves and powerful magnets to take pictures of bone and bone marrow
• Shows abnormal areas where myeloma cells have replaced bone marrow
• May be given if the bone survey does not show any problems
Low-dose CT scan
• Using x-rays, takes many pictures of a body part from different angles; then all
pictures are combined to make one clear picture
• Recommended because it shows the presence of lytic bone lesions (spots where
the bone looks as if it has been eaten away). These lesions, which are common in
multiple myeloma, may cause pain and weaken the bones
PET/CT scan
• Shows how cells are using a simple form of sugar
• To create pictures, a sugar radiotracer emits a small amount of energy that is
detected by the machine that takes pictures
• Myeloma cells appear brighter in the pictures because they use sugar more quickly
than normal cells
• A PET scan is very good at showing active myeloma and how far it has spread. It
can also help show bone damage from myeloma
Echocardiogram
• Imaging test of heart function
• Uses sound waves to make pictures
National Comprehensive Cancer Network (2019). NCCN Guidelines for Patients®: multiple myeloma. Version 2.2019.
Available at: http://www.nccn.org/patients

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D. ADDITIONAL TESTS
Urine Tests
Total protein
• Measures the total amount and type of protein in urine
• Urine is collected over a 24-hour period
• Can show the amount of light chains, also called Bence
Jones protein, in the urine. This helps to measure the tumor
burden in patients with myeloma cells that primarily or
exclusively make light chains
UPEP
• Measures the amount of M-proteins in the urine
• Urine is collected for 24 hours to assess the tumor burden
• Administered when myeloma is first found; it may also be
repeated to check how well treatment is working
UIFE
• Identifies the type of M-proteins present in urine to assess
the tumor burden
• Administered when myeloma is first found; it may also be
repeated to check how well treatment is working
Tissue Tests
Bone marrow biopsy and aspiration
• Biopsy: removes a small piece of solid bone and bone
marrow
• Aspiration: removes a small amount of liquid bone marrow
• Often, both tests are done at the same time on the back of
the hip bone
Tissue biopsy
• For a solitary plasmacytoma, a tissue biopsy may be done
to remove a sample of the mass for testing
• The sample is often removed via a fine-needle aspiration
(FNA) biopsy, which uses a very thin needle to remove a
small sample from the mass, or with a core needle biopsy,
which uses a larger needle to collect a larger sample of
tissue
• For a tissue biopsy, an imaging test may be used to guide
the needle through the skin and into the mass

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Laboratory Tests
Flow cytometry
• Measures the amount of myeloma cells in the bone marrow
• Can distinguish between normal plasma cells and abnormal plasma cells
(myeloma cells)
Immunohistochemistry
• Performed on the bone marrow biopsy sample
• Measures the number of myeloma cells in the bone marrow
Genetic tests
• Used to check for abnormal chromosomes and genes
• Bone marrow cells are grown in the laboratory to make the cells divide so that
the dividing cells can be examined
• Cytogenetic testing: uses a microscope to examine the chromosomes inside
myeloma cells to look for abnormal changes. This is done on a sample of
bone marrow
• Karyotyping: while examining the cells, a pathologist will also look at a “map”
of the chromosomes under a microscope. This will show any abnormal
changes in the size, shape, structure, or number of chromosomes
• FISH: uses probes that attach to certain parts of the chromosomes known to
be affected in myeloma. It can determine whether the myeloma is considered
standard risk or high risk
• Gene expression testing: looks for certain genes that may be turned on or off
in myeloma cells. This is not routinely performed
Plasma cell proliferation
• Shows what percentage of the myeloma cells are dividing
• A larger number of cells dividing is a sign that the cancer will grow rapidly
Light chain amyloidosis
• Amyloid is a rare protein found in people with abnormal plasma cells that
make abnormally folded light chains
• Amyloidosis: amyloid builds up in tissues and organs throughout the body,
damaging organs such as the heart and kidneys
• Tests for light chain amyloidosis can be done on a biopsy of the bone marrow,
fat pad (fat from just under the skin of the belly), or another organ that has
amyloid deposits
National Comprehensive Cancer Network (2019). NCCN Guidelines for Patients®: multiple myeloma. Version 2.2019.
Available at: http://www.nccn.org/patients

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Tests That May Be Useful for Some Patients
Tissue biopsy for solitary plasmacytoma
Plasma cell proliferation
Whole-body or skeletal magnetic resonance imaging (MRI)
Whole-body fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan
Serum viscosity
Human leukocyte antigen (HLA)
Echocardiogram
Evaluation for light chain amyloidosis
National Comprehensive Cancer Network (2019). NCCN Guidelines for Patients®: multiple myeloma. Version 2.2019.
Available at: http://www.nccn.org/patients

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II. MULTIPLE MYELOMA: STAGING
Stage Durie-Salmon Staging System Revised International Staging System
I
• Hemoglobin >19.5 g/dL
• Serum calcium value normal or ≤12 mg/dL
• X-ray studies of bone show normal bone
structure (scale 0) or solitary bone
plasmacytoma only
• Low M-component production rate
• IgG value <5 g/dL; IgA value <3 g/dL
• Urine light chains <4 g over 24 hours
• Serum albumin >3.5 g/dL
• Serum beta-microglobulin <3.5 mg/L
• No high-risk cytogenetics
• Normal serum lactate dehydrogenase
level
II
• Neither stage 1 nor stage III
• A: No renal failure (creatinine ≤2 mg/dL)
• B: Renal failure (creatinine >2 mg/dL)
• Neither stage I nor stage III
III
• Hemoglobin value <8.5 g/dL
• Serum calcium value >12 mg/dL
• X-ray studies of bone show >3 lytic bone
lesions
• High M-component production rate
• IgG value >7 g/dL; IgA value >5 g/dL
• Urine light chains >12 g over 24 hours
• Serum beta-microglobulin >5.5 mg/L
• High-risk cytogenetics:
• t(4;14)
• t(14;16)
• del(17p)
IgG = immunoglobulin G; IgA = immunoglobulin A.
Leukemia & Lymphoma Society (2019). Myeloma staging. Available at: https://www.lls.org/disease-
information/myeloma/diagnosis/myeloma-staging

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III. TREATMENTS FOR MULTIPLE MYELOMA
Types of Systemic Therapies
Proteasome inhibitor
(targeted therapy)
• Bortezomib (Velcade®
)
• Carfilzomib (Kyprolis®
)
• Ixazomib (Ninlaro®
)
Histone deacetylase (HDAC)
inhibitor (targeted therapy)
• Panobinostat (Farydak®
)
Chemotherapy
• Bendamustine (Bendeka™, Treanda®
)
• Cisplatin (Platinol®
)
• Cyclophosphamide (Cytoxan®
)
• Doxorubicin hydrochloride (Adriamycin®
)
• Doxorubicin hydrochloride liposome (Doxil®
)
• Etoposide (Etopophos®
)
• Melphalan (Alkeran®
)
Monoclonal antibody
• Daratumumab (Darzalex®
)
• Elotuzumab (Empliciti™)
Steroid • Dexamethasone (Decadron®
)
Immunomodulator
• Lenalidomide (Revlimid®
)
• Pomalidomide (Pomalyst®
)
• Thalidomide (Thalomid®
)
Additional Treatment Methods
Radiation Therapy
• Treats cancer cells in one small, specific area of the body
• Most commonly used to treat an area of bone damage that is painful or a
plasmacytoma (a single mass of myeloma cells) that is causing pain
• Can be used as the only treatment for solitary plasmacytomas
• Common side effects: nausea, diarrhea, fatigue, decrease in appetite,
weight loss, changes in skin and hair loss in treated area
Surgery
• Used to remove a solitary plasmacytoma located outside of the bone if it is
causing symptoms and cannot be treated with radiation alone
• Radiation therapy may be given before or after the surgery
• Surgery may also be used to fix bone fractures caused by myeloma
• Common side effects: weakness, tiredness, pain after surgery, swelling,
surgical scars, infections (less frequent)
National Comprehensive Cancer Network (2019). NCCN Guidelines for Patients®: multiple myeloma. Version 2.2019.
Available at: http://www.nccn.org/patients

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IV. COMBINATION THERAPIES FOR MULTIPLE MYELOMA
Therapeutic Combinations
Preferred Options
• Bortezomib/lenalidomide/dexamethasone
• Carfilzomib (twice weekly)/dexamethasone
• Carfilzomib (weekly)/dexamethasone
• Carfilzomib/lenalidomide/dexamethasone
• Daratumumab/bortezomib/dexamethasone
• Daratumumab/lenalidomide/dexamethasone
• Elotuzumab/lenalidomide/dexamethasone
• Ixazomib/lenalidomide/dexamethasone
Additional
Options
• Bendamustine/bortezomib/dexamethasone
• Bendamustine/lenalidomide/dexamethasone
• Bortezomib/liposomal doxorubicin/dexamethasone
• Bortezomib/cyclophosphamide/dexamethasone
• Carfilzomib/cyclophosphamide/dexamethasone
• Cyclophosphamide/lenalidomide/dexamethasone
• Bortezomib/dexamethasone
• Daratumumab
• Daratumumab/pomalidomide/dexamethasone
• Elotuzumab/bortezomib/dexamethasone
• Elotuzumab/pomalidomide/dexamethasone
• Ixazomib/dexamethasone
• Ixazomib/pomalidomide/dexamethasone
• Lenalidomide/dexamethasone
• Panobinostat/bortezomib/dexamethasone
• Panobinostat/carfilzomib
• Panobinostat/lenalidomide/dexamethasone
• Pomalidomide/cyclophosphamide/dexamethasone
• Pomalidomide/dexamethasone
• Pomalidomide/bortezomib/dexamethasone
• Pomalidomide/carfilzomib/dexamethasone
Useful for Some
Patients
• Dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/toposide/
bortezomib
• High-dose cyclophosphamide
National Comprehensive Cancer Network (2019). NCCN Guidelines for Patients®: multiple myeloma. Version 2.2019.
Available at: http://www.nccn.org/patients

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V. MULTIPLE MYELOMA: STEM CELL TRANSPLANT
Type of
Transplant
Description
Autologous stem
cell transplant
• Most common type of transplant used for active (symptomatic) myeloma
• Uses patient’s own blood stem cells, collected after primary treatment or high-dose
therapy
• The intent is to use high doses of chemotherapy to kill the maximum amount of
myeloma cells and then help the bone marrow recover by putting the blood stem
cells back into the bloodstream. From there, they travel to the bone marrow and
grow
Tandem stem cell
transplant
• A second stem cell transplant, given after a planned second round of high-dose
chemotherapy following the first autologous transplant
• The second transplant can be an autologous or allogeneic and is typically done
within 6 months after the first transplant
Allogeneic stem
cell transplant
• Uses blood stem cells from a donor who matches the patient’s HLA typing
• Graft-versus-tumor (GVT) activity: myeloma cells are attacked by the transplanted
donor blood stem cells
• Used infrequently because of the difficulty in finding a matching donor, serious side
effects (can include death), and high risk of myeloma recurrence
Donor lymphocyte
infusion
• The patient receives lymphocytes (white blood cells that help the body fight
infections) from the same person who donated blood stem cells for the original
allogeneic transplant
• The purpose of a donor lymphocyte infusion is to stimulate the GVT effect
• May be given if the myeloma returns after the first allogeneic stem cell transplant
Mini transplant
• A type of allogeneic transplant
• Called a “mini” transplant because lower doses of chemotherapy, radiation therapy,
or both are given before the transplant
• Goal: retain the GVT effect with less severe side effects
National Comprehensive Cancer Network (2019). NCCN Guidelines for Patients®: multiple myeloma. Version 2.2019.
Available at: http://www.nccn.org/patients

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VI. MULTIPLE MYELOMA: SUPPORTIVE CARE
Bone Damage
Bisphosphonates
• Used to strengthen bones and reduce risk of bone problems
• Administered intravenously
• Pamidronate (Aredia®
)
Denosumab (Xgeva®)
• Can prevent bone problems
• Given as an injection under the skin for 4 weeks
• May cause osteonecrosis of the jaw
Surgical Procedures
• Surgery may be used to treat fractures
• Orthopedic surgeons may place a rod to support the bone and hold it in
place
• Vertebroplasty for compression fractures: cement is injected into the bones
to relieve pain and hold the bones in place
• Kyphoplasty: a balloon-like device is placed in the fractured vertebra and
then inflated to spread out the vertebrae in order to achieve normal spine
shape and height. The balloon is then removed, and a type of cement is
injected to support the vertebrae
Radiation therapy • Can be used to treat pain from bone damage
Kidneys
Calcium in the bloodstream
• Myeloma causes calcium to be released from the bones into the
bloodstream. This is dangerous for the kidneys
• Intravenous (IV) fluids can help the kidneys flush out calcium
Hyperviscosity
• Blood thickens due to high levels of M-proteins, causing damage to
kidneys and other organs
• Can be treated by plasmapheresis (filtering blood through a machine
to remove M-proteins)
Myeloma kidney
• High levels of abnormal M-proteins, including light chains, can also
damage the kidneys
• Free light chains combine with another protein in the kidneys, causing
them to be too large to pass through the kidneys
• Myeloma must be treated to avoid myeloma kidney
National Comprehensive Cancer Network (2019). NCCN Guidelines for Patients®: multiple myeloma. Version 2.2019.
Available at: http://www.nccn.org/patients

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Other Treatment-Related Adverse Events
Anemia
• Myeloma cells may crowd out the normal blood cells in the blood marrow, which can
cause anemia (a condition in which the red blood cell count is too low)
• Can be treated with erythropoietin, a drug which helps the bone marrow to make more
red blood cells
Infections
• Myeloma and certain myeloma treatments can increase the risk of infection
• This risk can be reduced by vaccines for pneumonia, influenza, and shingles
• Intravenous immunoglobulins may be given to prevent frequent and serious infections
Shingles
• An infection that causes a painful skin rash
• Can be a side effect of bortezomib, carfilzomib, ixazomib, or daratumumab
• Treated with antivirals and nerve pain medications. These may also be given as a
preventative measure at the beginning of myeloma treatment
Blood clots
• Drugs that can cause blood clots: thalidomide, lenalidomide, and pomalidomide
• Treatment with blood thinners or antiplatelet agents may be needed if these drugs are
used
National Comprehensive Cancer Network (2019). NCCN Guidelines for Patients®: multiple myeloma. Version 2.2019.
Available at: http://www.nccn.org/patients