Warning signs of myeloma
Any ONE of these early warning signs could indicate myeloma:
¡ Bone pain (persistent or recurrent)
¡ Back pain (persistent or recurrent)
¡ Fatigue (unexplained progressive tiredness)
A correct diagnosis of myeloma that is made earlier in the disease course can result in earlier treatment and fewer secondary complications. A study found that when a patient is diagnosed by a primary care doctor, the typical diagnostic interval is more than 6 months. When a patient is diagnosed by a hematologist-oncologist, the typical diagnostic interval is less than 3 months.
Myeloma is a highly individual disease. It can be slow-moving or aggressive. A local hematologist-oncologist might see a few myeloma patients or none at all. This is why it has become commonplace for a local doctor to collaborate with a myeloma specialist in administering the care of a patient with myeloma. The field of myeloma is evolving at an unprecedented pace and the treatment options are expanding like never before.
A myeloma specialist can make the correct diagnosis in a timely manner and tailor the optimal treatment approach best suited to the individual
Figure 2. Plasma cells in the bone marrow
healthy bone marrow multiple myeloma
regular number of healthy plasma cells and normal antibodies
plasma cells transform into myeloma cells
uncontrolled proliferation of myeloma cells and abnormal antibodies
patient. Myeloma specialists at large “high-volume” treatment centers or academic institutions treat hundreds of myeloma patients, conduct clinical trials with new drugs and new combination therapies, and develop the expertise needed to help you make good decisions about your care in partnership with your doctor.
CRAB criteria
See Table 2 for the effects of increased myeloma cells in the bone marrow. Any ONE of the CRAB criteria could indicate myeloma:
¡ Calcium – elevated level in the blood,
¡ Renal (kidney) impairment – elevated creatinine,
¡ Anemia – low red blood cell count,
¡ Bone damage.
Start with these THREE screening tests
Efficient testing can save myeloma patients from delayed diagnosis and secondary complications. When ALL three of these low-cost and accurate tests are used together, they will identify 99% of myeloma cases:
1. Serum free light-chain (sFLC) test,
2. Serum protein electrophoresis (SPEP), and
3. Immunofixation electrophoresis (IFE).
When the SPEP test is used alone (without sFLC and IFE), 1 out of 8 cases of myeloma will not be detected. Be sure to get all THREE of these accurate and cost-effective screening tests if myeloma is suspected.
Important testing in myeloma
Many tests and techniques are used to diagnose, monitor, and assess myeloma status throughout the disease course. Test results best reflect a myeloma patient’s status when followed and reviewed over time. No single test is adequate to tell the whole story of a patient’s current myeloma status.
A trend or pattern reveals more than a single test result or study. Each test can be thought of as a piece of a puzzle; only when the pieces are assembled correctly can a patient and an experienced myeloma specialist make the proper inferences and decisions.
Baseline (initial) testing of a newly diagnosed myeloma patient must be gathered so that it can be used for comparison with later data. Baseline testing should include the sFLC test, bone marrow biopsy, and MRI scan.
Important note: Do NOT compare your test results to those of other patients as each case of myeloma is unique.
Figure 3. Structures of immunoglobulins
Table 2. Effects of increased myeloma cells in bone marrow
CRAB CRITERIA
C – Calcium levels in the blood are increased
CAUSE IMPACT ON PATIENT
Release of calcium from damaged bone into the bloodstream.
R – Renal problems –kidney damage
A – Anemia
B – Bone damage
• Thinning (osteoporosis) or
• Areas of more severe damage (lytic lesions), fracture, or collapse of a vertebra
Other types of organ dysfunction
Abnormal immune function
M-proteins can pass from the bloodstream into the urine, causing kidney damage. High blood calcium, infections, and other factors can also cause or increase kidney damage.
Decrease in number and activity of red blood cell-producing cells in the bone marrow.
The myeloma cells activate osteoclast cells, which destroy bone and block osteoblast cells, which normally repair damaged bone.
Local or systemic effects of myeloma, other than CRAB features.
The myeloma cells reduce the number and activity of normal plasma cells capable of producing antibodies against infection.
• Mental confusion
• Dehydration
• Constipation
• Fatigue
• Weakness
• Renal (kidney) damage
• Impaired circulation
• Fatigue
• Mental confusion
• Fatigue
• Weakness
• Bone pain
• Fracture or collapse of a bone
• Nerve or spinal cord damage
• Neuropathy
• Recurrent infections
• Bleeding problems
• Other individual problems
• Susceptibility to infection
• Delayed recovery from infection
• Reduced response to vaccination
Blood and urine tests
¡ Complete blood count (CBC) testing is used to measure the three key blood cells:
¡ red blood cells (RBC) that carry oxygen,
¡ white blood cells (WBC) that form part of the immune system, and
¡ platelets that help with blood clotting.
¡ The chemistry panel evaluates several chemicals in the blood, including electrolytes (e.g., sodium, chloride), creatinine and BUN (to assess kidney function), and AST and ALT (to assess liver function).
¡ The serum albumin (sALB) test measures normal protein in the blood.
Figure 4. Healthy bone compared to myeloma bone
¡ The beta-2 microglobulin (β2-microglobulin, β2M, or β2M) test measures a small protein that is a tumor marker in myeloma. It is detected in the blood by the serum β2M test (sβ2M).
¡ The serum lactate dehydrogenase (sLDH) test measures the level of an enzyme used to monitor myeloma activity.
¡ The serum protein electrophoresis (SPEP) and the urine protein electrophoresis (UPEP) tests are used in both diagnosing and monitoring myeloma. These tests enable both the calculation of M-protein amount and the identification of the type of monoclonal spike for each patient. The M-spike, a sharp pattern that occurs on protein electrophoresis tests, is a marker for the activity of myeloma cells – see Figure 5.
¡ The immunofixation electrophoresis (IFE) test of the serum (sIFE) or urine (uIFE) identifies the types of the M-protein: heavy chain (G, A, D, E, or M) and the light chain (kappa or lambda).
¡ The serum free light-chain (sFLC) test assesses the kappa light-chain level, the lambda light-chain level, and the kappa/lambda ratio produced by the myeloma cells. Measuring the output of myeloma cells is an indirect but effective way to assess the amount and activity of the cancer.
+ Myeloma cells Lytic lesion
HEALTHY BONE
MULTIPLE MYELOMA
¡ C-reactive protein (CRP) is made in the liver. It increases in amount when there is inflammation throughout the body.
Cytogenetics
Cytogenetics (karyotyping) testing detects missing, rearranged, or extra chromosomes (strands of DNA and proteins in the nucleus of a cell). Cytogenetic tests do not measure your inherent genetics, but rather they assess the chromosomes in your plasma cells, providing important information about your myeloma and helping to determine if your myeloma should be classified as “high-risk” or not.
The fluorescence in situ hybridization (FISH) testing is the assessment of the chromosomes of all myeloma cells in a bone marrow sample. FISH testing can detect the presence of translocations, missing pieces, extra pieces, and loss of chromosomes. FISH can detect changes regardless of whether myeloma cells are growing or not. Special gene probes that fluoresce (glow) are added to the bone marrow sample. These probes track genetic material after cell division and signal the presence or absence of chromosomal abnormalities that are known to occur in myeloma.
Figure 5. SPEP test results albumin
Normal SPEP result
Abnormal result with myeloma cells producing the M-protein, creating an M-spike in the beta-2 zone
Abnormal result with myeloma cells producing the M-protein, creating an M-spike in the gamma zone
Each chromosome is given probes of a different color. For example, if genetic material from chromosome 4 is wrongly connected to chromosome 14, then the differently colored dots of genetic material from these chromosomes appear together, indicating the high-risk abnormality t(4;14), which stands for “translocation of genetic material between chromosomes 4 and 14.” Other abnormalities that are considered high-risk in myeloma are t(14;16) and t(14;20), del(17p) which stands for “deletion of the short arm (upper part) of chromosome 17,” and +1q which stands for “a gain in the long arm (lower part) of chromosome 1.”
Bone marrow testing
Myeloma is a cancer of the bone marrow, so it is critical to test the bone marrow to make the diagnosis. This testing helps assess the percentage of plasma cells in the bone marrow and the general marrow function. Bone marrow testing is repeated again when myeloma relapses.
Bone marrow aspiration is the removal, by a needle, of a sample of fluid and cells from the bone marrow for examination under a microscope. Bone marrow biopsy is the removal, by a hollow-bore needle, of a sample of tissue from the bone itself – see Figure 6. Both the bone marrow aspiration and the bone marrow biopsy are usually done at the same time.
Bone testing
The following bone testing techniques are listed in alphabetical order:
¡ Bone density testing is a method of assessing bone integrity, osteopenia, and osteoporosis.
¡ Computed axial tomography (CAT or CT) scanning is commonly used in myeloma to assess the bones. A whole-body low-dose CT (WBLDCT) scan is preferred due to reduced radiation exposure.
¡ Magnetic resonance imaging (MRI) is a sensitive test that can assess anatomy very precisely and is particularly helpful in myeloma for assessing spinal or bone marrow involvement.
¡ Nuclear imaging is rarely used in myeloma as it is not sensitive to detecting myeloma bone disease.
¡ Positron emission tomography (PET) scanning is a very sensitive technique that uses the technology of CT scans but adds the ability to assess for cellular activity. This can be particularly helpful in patients with extramedullary disease (EMD), whose myeloma is outside of the bone or bone marrow.
¡ X-rays were used in years past to assess myeloma bone disease, often with a test called the “skeletal survey,” but X-rays are no longer
Site of biopsy
Bone marrow Bone Skin
© 2015
Slaybaugh Studios
Figure 6. Bone marrow biopsy
recommended in myeloma because they cannot detect damage until it has become extensive.
For a more in-depth discussion of tests used in myeloma, read the IMF’s publication Understanding Your Test Results.
IMWG diagnostic criteria
The IMF International Myeloma Working Group (IMWG), the research arm of the IMF, has published guidelines that the diagnosis of active myeloma must include both of the following:
1. Presence of monoclonal plasma cells in the bone marrow ≥ 10% or biopsy-proven bony or extramedullary plasmacytoma (a tumor of monoclonal plasma cells that is found in soft tissue outside of the bone marrow and separate from bone).
2. Evidence of at least ONE myeloma-defining event (MDE):
¡ Presence of CRAB criteria.
¡ Presence of monoclonal plasma cells in the bone marrow ≥ 60%.
¡ Ratio of involved-to-uninvolved sFLC ≥ 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. (Uninvolved light chains are those that are not made by myeloma cells.)
¡ One or more focal lesions seen on MRI scan.
¡ One or more lytic lesions on CT or PET-CT.
The presence of any one MDE indicates active disease and the need for treatment.
PROGNOSTIC FACTOR
International Staging System (ISS)
Chromosomal abnormalities (CA) by FISH
Serum lactate dehydrogenase (sLDH)
Revised International Staging System (R-ISS)
CRITERIA
Stage I sβ2M < 3.5 mg/L, sALB ≥ 3.5 g/dL
Stage II Not ISS stage I or III
Stage III sβ2M ≥ 5.5 mg/L
high-risk One or more CA: del(17p), t(4;14), t(14;16)
standard-risk No high-risk CA
normal sLDH is lower than the upper limit of normal high sLDH is higher than the upper limit of normal
Stage I ISS stage I, standard-risk CA by FISH, and normal LDH
Stage II Not R-ISS stage I or III
Stage III ISS stage III and either high-risk CA by FISH or high LDH FISH (fluorescence in situ hybridization), sβ2M (serum beta-2 microglobulin); sALB (serum albumin).
Table 3. Risk stratification of myeloma
Staging of myeloma
The stage of myeloma varies from patient to patient at the time of diagnosis. The staging system for myeloma continues to evolve – see Table 3. Staging is a prognostication tool based on values used to provide guidance to clinicians in the evaluation and treatment of myeloma.
In 1975, the Durie-Salmon Staging System was introduced to classify patients with myeloma based on the correlation between the amount of myeloma and the damage caused by it.
In 2005, the IMWG developed the International Staging System (ISS) to assess disease behavior that is most predictive of HRMM based on four markers of aggressive disease: sβ2M, sALB, sLDH, and CRP.
In 2015, the IMWG published the Revised International Staging System (R-ISS), combining ISS with two strongly recommended tests for chromosomal abnormalities, which are performed on bone marrow samples taken at the time of diagnosis: cytogenetics (karyotyping) and FISH.
At the time of this printing, the newly updated version of the R-ISS is being prepared by IMWG researchers for upcoming publication in a medical journal. Once this information is no longer embargoed, it will be included on the IMF website at myeloma.org/tests-staging.
Types of myeloma
Each patient’s myeloma cells produce only 1 of the following 5 types of immunoglobulin proteins: IgG, IgA, IgD, IgE, and IgM. Each immunoglobulin is made up of two heavy chains bound to two light chains. The two types of light chains are kappa (κ) and lambda (λ). Your type of myeloma is identified by the IFE test. Knowing your myeloma type is helpful to understanding your disease and its treatment.
IgG myeloma
Approximately 65% of myeloma patients have IgG myeloma with either kappa or lambda light chains. The behavior of IgG myeloma conforms to CRAB criteria features.
IgA myeloma
IgA myeloma is the second-most common type, also with either kappa or lambda light chains. Patients with IgA myeloma sometimes have tumors outside of the bone.
IgD, IgE, or IgM myelomas
These three types of myeloma are quite rare. IgD myeloma can be accompanied by plasma cell leukemia (PCL).
Understanding light chains
Approximately 50% of myeloma patients produce free light chains in addition to the complete molecule combination of light chains bound to heavy chains.
Approximately 15%–20% of myeloma patients produce only light chains and no heavy chains. This is called Bence-Jones myeloma, named for the English doctor who first detected and identified light chains, and published his findings in 1848.
Light-chain M-proteins are smaller and weigh less than heavy chains, making it possible for them to fit through the tiny capillaries that send blood to the kidneys. The light chains that arrive by blood to the kidneys may build up to the point of blocking the kidney’s tubules, causing reduced kidney function.
Table 4. Other plasma cell diseases related to myeloma
DISEASE TYPE DESCRIPTION
Waldenström macroglobulinemia (WM)
Amyloidosis:
AL or immunoglobulin
light chain type
κ or λ subtypes
Light Chain Deposition
Disease (LCDD):
κ or λ subtypes
POEMS syndrome:
Usually IgG or IgA λ (rarely κ subtype)
A hybrid-like disease between myeloma and lymphoma where there is an IgM monoclonal protein and bone marrow involvement of cells that are “lymphoplasmacytic.” WM must be differentiated from IgM myeloma. WM is treated more like lymphoma.
• Amyloidosis
The light chains are deposited in a linear fashion (β-pleated) in tissues rather than being broken down and/or excreted in the urine. There are many varieties of amyloidosis involving deposits of different types of protein. For example, Alzheimer’s disease involves deposits of proteins in the brain.
• Myeloma-related amyloid
Light chains can be deposited in many tissues, including skin, tongue, heart, kidneys, nerves, lungs, liver, and intestines. Tissues stain positive with a “congo red” dye test, which is diagnostic. More detailed testing with mass spectroscopy and/or electron microscopy may be appropriate and necessary.
The light chains are deposited in a disorganized crosslinked fashion. Tissues stain positively with direct κ or λ immunostaining. Congo red staining is usually negative. There are different patterns of tissue deposits often involving the kidneys, the lining of the lungs (pleura) or peritoneum (around intestines) or within the eyes.
A complex disorder involving polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes.
This is why patients with light-chain only myeloma are more likely to have kidney damage or deposits of light chains or on nerves or other organs.
In the majority of patients with light-chain myeloma, their disease can be measured with the sFLC test. In some patients, their myeloma can be measured only in the urine.
Only 1%–2% of myeloma patients produce very little or no M-protein of any type. These patients may have to be assessed by other means (e.g., imaging, bone marrow testing).
Figure 7. Osteoclasts and osteoblasts
Compac t bone Yellow marrow
Spongy bone containing red marrow
The goal of treatment is to normalize the light-chain levels, especially the ratio, and to eliminate the M-protein.
Osteoclast (breaks down bone)
Extramedullary disease (EMD)
Myeloma is primarily a disease of the bone marrow, but it can escape outside of the bone and to other parts of the body. Imaging studies are required to detect and monitor EMD. It may be higher risk and more aggressive than myeloma that is confined to the bone marrow.
See Table 4 for an overview of other plasma cell diseases related to myeloma.
Myeloma’s effects in the body
Inside the bone marrow
All the blood cells – white blood cells, red blood cells, and platelets – are made in the bone marrow. When myeloma grows in the bone marrow, the effects include a reduction in blood cell production. Anemia, a low level of red blood cells or hemoglobin, is an early and common sign of myeloma.
Cells in healthy bone marrow maintain our skeletons in a balanced state of bone breakdown and bone buildup. The presence of myeloma cells in the bone marrow stimulates the cells that break down bone (osteoclasts) and suppresses cells that build new bone (osteoblasts) – See Figure 7. This lack of balance results in bone pain, fractures, and the release of calcium into the blood.
Osteoblast (builds new bone)
Osteoc yte
Slaybaugh Studios
Outside the bone marrow
The release of calcium from bones into the bloodstream can result in hypercalcemia, a higher than normal level of calcium in the blood. Hypercalcemia can cause loss of appetite, nausea, thirst, fatigue, muscle weakness, restlessness, confusion, and other symptoms.
Both hypercalcemia and high levels of M-protein in the blood can seriously damage the kidneys, causing kidney failure. As myeloma cells build up in the bone marrow, M-protein is released into the circulating blood, which can cause tissue damage at distant sites (e.g., kidney damage).
M-protein can also interfere with blood clotting or circulation, potentially causing other organ or tissue damage (e.g., damage to nerve tissue).
Possible urgent problems at diagnosis
Upon diagnosis, the management of your myeloma is the top priority until remission has been achieved, except in cases of emergency medical problems. There are medical problems that require immediate attention before beginning systemic therapy for myeloma. These include compromised bony structures, nerve damage, infections, and kidney disease.
Along with the immediate management of the complications, a prompt consultation with a myeloma specialist is essential to ensure that any treatment of an urgent medical problem does not limit your options for the treatment of myeloma. For example, radiation therapy to shrink a plasmacytoma (tumor) that is pressing on nerve tissue must be weighed carefully against a surgical option, because radiation therapy may damage the bone marrow, thereby limiting your options for myeloma therapy.
Bony complications and nerve damage
Bony areas of lytic lesions, fractures, or collapsed vertebrae can cause bone pain and nerve or spinal cord damage. The vertebrae (bony segments of the spinal column) are often affected by myeloma. Because the spinal cord runs through the vertebrae, painful vertebral fractures may occur. In addition, myeloma tumors growing in the vertebrae can also press on spinal nerves. Nerve compression is not uncommon. Loss of motor nerves can cause paralysis.
Vertebral compression fractures (VCF) are a serious complication of myeloma. Treatments of VCFs include analgesics to relieve pain, bracing to provide temporary stability, and minimally invasive surgical procedures such as vertebral augmentation and balloon kyphoplasty. For more information about VCFs, read the IMF’s publication Understanding Treatment of Myeloma-Induced Vertebral Compression Fractures.
Infection
The growth of myeloma cells reduces the number and activity of normal plasma cells that produce antibodies against infection, leaving the patient susceptible to infection. Furthermore, as the marrow is taken over by myeloma cells, the production of normal cells, including infection-fighting white blood cells, can be reduced in number. Serious infections may occur, requiring immediate intervention.
Kidney damage or failure
Renal (kidney) damage or failure can cause dramatic fatigue and weakness, mental confusion, and decrease or lack of urination. Treatments range from hydration to dialysis.
Blood clots and thromboembolic events
Clotting events may be medical emergencies. Treatment is based on patient risk factors, location of the clot, and potential impact on local and distant tissues.
Your healthcare team
Studies have shown that a positive relationship between the patient and the healthcare team is associated with improved survival in cancer. Also, it has been demonstrated that optimal patient care occurs when there is effective communication among all members of the patient’s healthcare team. In myeloma, the central member of such a team is the myeloma specialist, but your healthcare team may also include your primary care physician, nurse or nurse practitioner, orthopedic surgeon (bone specialist), nephrologist (kidney specialist), dentist or oral surgeon, and pharmacist.
When to begin treatment of myeloma
The most important initial decision is when to begin treatment for your myeloma. The urgency of starting treatment depends upon the exact problems faced by an individual patient. This is why the experience and expertise of a myeloma specialist is of such importance.
Understanding the results of your baseline testing, as well as the staging and prognostic classification of your myeloma will help you make the decision about initiating treatment.
FDA-approved drugs used to treat myeloma
Many highly effective therapies are approved for treatment of myeloma by the U.S. Food and Drug Administration (FDA). Myeloma research is a robust field, with numerous clinical trials taking place around the world to add more promising approaches to the growing list of treatment options.
CD3 on the surface of the T cell
Figure 8. Bispecific antibody mechanism of action
bispecific antibody
bispecific antibody binds to CD3
bispecific antibody binds to tumor-specific antigen
tumor-specific antigen on the surface of the myeloma cell
bispecific antibody activates the T cell to release cytotoxic granules that kill the myeloma cell
A drug class is a group of medications that have a similar chemical structure or a similar mechanism of action (MOA). The MOA is the biochemical interaction or process through which a drug or a molecule induces its effect in the body. Listed below in alphabetical order are the drug classes currently used in the treatment of myeloma, as well as the individual drugs in each class and their FDA-approved indications.
New drugs and drug combinations are typically first approved by the FDA to be used for relapsed or refractory multiple myeloma (RRMM). An approval by the FDA of a frontline therapy for newly diagnosed multiple myeloma (NDMM) typically requires clinical trial data that demonstrates the drug’s efficacy and safety after comparing it to standard of care (SOC) therapy, a benchmark treatment that is widely accepted by medical experts as the most appropriate. Frontline therapy is the initial treatment used in an effort to achieve response in a patient with NDMM.
Please note that if a particular therapy is not working for you, there may be numerous other available treatment options. However, it is not advisable to rapidly skip from one treatment regimen to another.
Alkylating agents
Chemotherapy is any drug or combination of drugs used to kill cancer cells. An alkylating agent is a chemotherapeutic agent that crosslinks the DNA of myeloma cells and blocks cell division. Alkylating agents were the earliest effective drugs used in the treatment of myeloma, with melphalan first synthesized in 1953 and first used to treat myeloma in 1962. Cyclophosphamide and bendamustine are two other alkylating agents currently used in myeloma.
Bispecific antibodies (bsAb)
An artificial antibody that binds to two (“bi”) targeted cells, typically one antigen on the myeloma cell and another antigen on an immune cell, such as a T cell or natural killer (NK) cell – see Figure 8.
¡ Elrexfio™ (elranatamab-bcmm) is FDA-approved for the treatment of RRMM after at least 4 prior lines of therapy. For more information, read the IMF’s publication Understanding ELREXFIO™ (elranatamab-bcmm).
¡ Talvey ® (talquetamab-tgvs) is FDA-approved for the treatment of RRMM after at least 4 prior lines of therapy. For more information, read the IMF’s publication Understanding TALVEY® (talquetamab-tgvs).
¡ Tecvayli® (teclistamab-cqyv) is FDA-approved for the treatment of RRMM after at least 4 prior lines of therapy. For more information, read the IMF’s publication Understanding TECVAYLI® (teclistmab-cqyv).
CAR T-cell therapy
Chimeric antigen receptor (CAR) T-cell therapy is an immunotherapy, treatment that enhances the body’s natural defenses to fight cancer. This approach involves collecting the patient’s T cells, engineering them to attack the patient’s own cancer cells, and reinfusing them into the patient –see Figure 9.
T cells are (1) collected from the patient’s bloodstream, (2) modified to produce receptors that recognize the patient’s myeloma cells, (3) multiplied in a laboratory in large numbers, (4) re-infused into the patient, (5) and the engineered T cells begin to destroy the patient’s myeloma cells.
Figure 9. CAR T-cell therapy mechanism of action
¡ Abecma® (idecabtagene vicleucel) is FDA-approved for the treatment of RRMM after at least 2 prior lines of therapy. For more information, read the IMF’s publication Understanding ABECMA® (idecabtagene vicleucel).
¡ Carvykti® (ciltacabtagene autoleucel) is FDA-approved for the treatment of RRMM after at least 1 prior line of therapy. For more information, read the IMF’s publication Understanding CARVYKTI® (ciltacabtagene autoleucel).
Immunomodulatory agents
An immunomodulatory agent is a drug that can modify, enhance, or suppress the functioning of the immune system. 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. Thalidomide is now infrequently used in the U.S., as it has given rise to a next generation of immunomodulatory agents with increased efficacy and reduced side effects.
¡ Pomalyst® (pomalidomide) is FDA-approved for the treatment of RRMM after at least 2 prior lines of therapy. For more information, read the IMF’s publication Understanding POMALYST® (pomalidomide).
¡ Revlimid® (lenalidomide) is FDA-approved for use throughout the myeloma disease course. For more information, read the IMF’s publication Understanding REVLIMID® (lenalidomide).
¡ Thalidomide is the generic drug name of this medication, which is also marketed under the brand name Thalomid®. Though used infrequently in the U.S., it is still sometimes used during the later stages of disease, in cases of renal failure, or when the patient has low blood counts. It is sometimes used in induction therapy and consolidation therapy. For more information, read the IMF’s publication Understanding Thalidomide Therapy in Myeloma.
Monoclonal antibodies (mAb)
Manufactured in a lab rather than produced in the human body, monoclonal antibodies are specifically designed to find and bind to cancer cells 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.
¡ Darzalex ® (daratumumab) and Darzalex Faspro® (daratumumab + hyaluronidase-fihj) are FDA-approved for use throughout the myeloma disease course. For more information, read the IMF’s publication Understanding DARZALEX® (daratumumab) intravenous infusion and DARZALEX FASPRO® (daratumumab + hyaluronidase-fihj) subcutaneous injection.
¡ Empliciti® (elotuzumab) is FDA-approved for the treatment of RRMM after at least 1 prior therapy. For more information, read the IMF’s publication Understanding EMPLICITI® (elotuzumab).
¡ Sarclisa® (isatuximab-irfc) is FDA-approved for use throughout the myeloma disease course. For more information, read the IMF’s publication Understanding SARCLISA® (isatuximab-irfc).
Proteasome inhibitors (PI)
A proteasome inhibitor is any drug that interferes with the normal function of the proteasome. A proteasome is a joined group (“complex”) of enzymes (“proteases”) that breaks 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, which is important for maintaining balance within the cell and for regulating cell growth.
¡ Kyprolis® (carfilzomib) is FDA-approved for the treatment of RRMM after at least 1 prior therapy. For more information, read the IMF’s publication Understanding KYPROLIS® (carfilzomib).
¡ Ninlaro® (ixazomib) is FDA-approved for the treatment of RRMM after at least 1 prior therapy. For more information, read the IMF’s publication Understanding NINLARO® (ixazomib).
¡ Velcade® (bortezomib) is FDA-approved for use throughout the myeloma disease course. For more information, read the IMF’s publication Understanding VELCADE® (bortezomib).
Selective inhibitor of nuclear export (SINE)
The first and only medication in the SINE drug class that has been approved by the FDA to treat myeloma is Xpovio® (selinexor). It works by preventing myeloma cells from expelling tumor suppressor proteins that help protect the cell from cancer. The forced nuclear retention of these proteins can counteract the pathways that allow cancer cells to continue to grow and divide. Xpovio is FDA-approved for the treatment of RRMM after at least 1 prior therapy. For more information, read the IMF’s publication Understanding XPOVIO® (selinexor).
Steroids
A steroid is a type of hormone. Steroidal hormones are produced by the body, and the synthetic analogues (equivalents) of some steroids can be manufactured in a laboratory. Dexamethasone is a synthetic adrenocortical steroid that has multiple effects and is used for many conditions. Dexamethasone is the generic drug name of this medication, which is also marketed
1. Induction therapy is given to prepare patient for ASCT.
2. Stem cells are mobilized from the bone marrow into the bloodstream.
3. Stem cells are collected from the bloodstream, frozen, and stored in a laboratory.
4. Patient is treated with high-dose chemotherapy to kill remaining cancer cells.
5. Stem cells are thawed and infused back into the patient through a vein.
6. Stem cells travel to the bone marrow and begin producing new blood cells.
under multiple brand names. Dexamethasone is one of the most frequently used medications in the treatment of myeloma, typically given in combination with other agents. For more information, read the IMF’s publication Understanding Dexamethasone in the Treatment of Myeloma.
Autologous stem cell transplant (ASCT)
ASCT has been used as a treatment for myeloma for several decades. The medical term for ASCT is “high-dose therapy (HDT) with stem cell rescue.” In patients with myeloma, the myeloma cells are intermixed in the same bone marrow microenvironment as the normal stem cells.
HDT is more effective at killing myeloma cells in the bone marrow than standard-dose chemotherapy, but HDT is also capable of damaging your normal stem cells. In the ASCT procedure, your stem cells are harvested (collected) before HDT has been administered, then reinfused (transplanted) into you to “rescue” your bone marrow from the effects of HDT.
For more information, see Figure 10 and read the IMF’s publication Understanding Stem Cell Transplant in Myeloma.
Selecting a myeloma treatment regimen
Before embarking on the treatment journey, discuss with your doctor the overall treatment strategy for your myeloma. It is important that you understand your treatment plan and have an active role in its selection. Below are some questions that may help facilitate a conversation with your doctor.
¡ Age: Does my age affect treatment selection and treatment outcome?
¡ Other medical issues: Will my other diagnoses affect my myeloma treatment?
¡ Treatment setting: Will I receive treatment at a clinic or take medication at home? What if I have a preference between inpatient or outpatient care?
¡ Transplant: Is an autologous transplant recommended in my case?
¡ Day-to-day functioning: Will treatment affect my daily activities, and my personal and professional obligations?
¡ Speed of response: How rapidly will the treatment work?
¡ Side effects: What are the treatment side effects? How can side effects be prevented or minimized?
¡ Financial considerations: What will be my financial responsibility? Which part of my treatment is covered by insurance? Are there resources to help me pay for treatment?
Treatment of myeloma bone disease
Approximately 70%–80% of patients with myeloma develop bone disease, which can cause bones to become thinner and weaker, and can create lytic lesions, which look like holes in the bone. The weakened bone is more likely to break due to minor pressures or injury. The bones most commonly affected are the spine, pelvis, ribs, skull, and the upper ends of the long bones of the arms and legs.
In a healthy skeleton, there is a balance between cells called osteoclasts (which break down bone tissue) and osteoblasts (which build new bone tissue). Myeloma cells cause osteoclasts to break down more bone tissue than is required for normal skeletal health while inhibiting the formation of osteoblasts and preventing the repair of bone loss.
In addition to causing bone disease, the process of accelerated bone breakdown releases calcium from the bones into the bloodstream, causing a condition called hypercalcemia, an elevated level of calcium in the blood.
Bone-modifying agents (BMA) help prevent bone damage and fractures, called skeletal-related events (SRE). BMAs have no anti-myeloma effect and do not prevent progression of early myeloma. BMAs can be safely combined with most myeloma therapies, although your doctor may decide not to give an intravenous BMA on or close to the day you receive IV therapy for your myeloma. Confirm with your doctor that the BMA you are receiving is not being combined with another drug that can harm your kidneys.
BMAs include bisphosphonates and a monoclonal antibody. For more information, read the IMF’s publication Understanding Treatment of Myeloma Bone Disease.
Bisphosphonates
Bisphosphonates are are recommended for all patients with myelomarelated bone disease. In 2018, the American Society of Clinical Oncology (ASCO) published updated guidelines on BMAs, recommending bisphosphonate therapy for all patients with myeloma that requires treatment, with or without evidence of lytic lesions or vertebral compression fractures (VCFs). Bisphosphonates are particularly helpful for myeloma patients being treated with steroids, which reduce bone density. Treatment with bisphosphonates inhibits and destroys osteoclasts, thereby reducing bone breakdown. When the myeloma is well controlled, bisphosphonates allow bone healing to occur.
¡ Aredia® (pamidronate) was FDA-approved in 1995. It is administered monthly by means of an intravenous (IV) infusion. The standard dose is 90 mg infused during 2–4 hours. In 2010, Lancet Oncology published the findings from a large clinical trial by the Nordic Myeloma Study Group (NMSG), which compared Aredia given at 30 mg to Aredia given at 90 mg. The study validated the efficacy of the reduced dose. Ask your doctor if Aredia at 30 mg dose is appropriate for your individual case.
¡ Zometa® (zoledronate) was FDA-approved in 2001. Zometa is administered monthly by means of an IV infusion. The standard dose is 4 mg infused during 15–45 minutes. The results of the Z-MARK clinical trial, published in 2016, showed that “the use of Zometa every 12 weeks compared with every 4 weeks did not result in an increased risk of skeletal events over 2 years.” The ASCO guidelines note that there are insufficient data to recommend a specific duration of bisphosphonate therapy beyond 2 years.
Bisphosphonates are excreted via the kidneys and can cause kidney toxicity. Toxicities associated with bisphosphonates are related to dosage, frequency of administration, and duration of infusion – any or all of which may be modified by your doctor.
Monoclonal antibody for bone disease
Xgeva® (denosumab) was FDA-approved in 2018 based on a clinical trial that demonstrated the non-inferiority of Xgeva when compared to Zometa. Xgeva blocks the ability of osteoclasts to mature, function, and survive. Xgeva produces a low level of kidney-related side effects when compared to bisphosphonates. The ASCO guidelines indicate that Xgeva may be preferable to bisphosphonates in patients with kidney damage. Xgeva is given as a subcutaneous (SQ) injection, a method of administering medication under the skin by a short needle that injects a drug into the tissue layer between skin and muscle.
Solitary plasmacytoma of bone (SPB)
SPB is a rare cancer of unknown origin. SPB is a single mass of monoclonal plasma cells in a bone or bone marrow. SPB is not myeloma, but it is important to note that the majority of people with SPB are eventually diagnosed with myeloma. SPB can be treated, and sometimes cured, with the use of radiation therapy or surgery.
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.
Fatigue
According to the National Cancer Institute (NCI), fatigue is the most common side effect of cancer treatment. Fatigue can also be caused by the myeloma itself, as well as by other medical conditions and their treatment.
The most common causes of fatigue in myeloma patients include anemia and persistent pain, which can result in weight loss, decreased appetite, and a sense of weakness. When more than one issue is present at the same time, fatigue can be severe.
If your anemia is severe, your doctor may recommend treatment with erythropoietin or a blood transfusion. For more information, read the IMF’s publication Understanding Fatigue in Myeloma.
Neuropathy
Neuropathy occurs when the nerves are damaged or inflamed, or when degeneration of nerve tissue has occurred, leading to changes in the way nerves function. The symptoms of nerve damage depend on the type of nerves affected (sensory, motor, or autonomic).
Some individuals who develop myeloma may have neuropathy from pre-existing conditions, such as diabetes or autoimmune diseases. Others can develop neuropathy when they are in the precursor state of MGUS. Patients with myeloma can develop neuropathy in the course of their disease or as a side effect of myeloma therapies.
Peripheral neuropathy (PN) is the most common type of neuropathy in patients with myeloma. PN is a condition that affects nerves in the feet, lower legs, arms, hands, and/or fingers. It is always best to prevent problems before they occur and to treat them early when they do occur. In many patients with myeloma, neuropathy is at least partially reversible. For more information, read the IMF’s publication Understanding Neuropathy in Myeloma.
Infections
Infections are a common and recurrent problem in patients with cancer. It is essential to have a strategy with your doctor to promptly bring infections under control. Antibiotics or antivirals may be necessary for an active infection, and prophylactic use can be considered if appropriate. Your doctor may prescribe medication to boost your white blood cell count. Intravenous immunoglobulin (IVIG) may be appropriate for severe infections.
Gastrointestinal side effects
Medications can treat nausea, vomiting, constipation, or diarrhea. Maintaining adequate fluid intake and nutrition is important. Severe symptoms may require hospitalization.
Other supportive care
In addition to the management of specific symptoms, other supportive care measures may be beneficial to alleviating the physical and emotional impact of living with myeloma.
Diet
No specific diet has been developed for myeloma patients, although research has clearly demonstrated a link between obesity and myeloma. In general, a healthy diet emphasizes “real” foods like fruits, vegetables, fish and other lean animal proteins, and whole grains. Avoid processed foods, added sugars, and trans fats. Use caution in these areas:
¡ Herbal and vitamin supplements – Check with your doctor or pharmacist before taking supplements while receiving treatment for myeloma. Some interactions between drugs and supplements may prevent myeloma treatments from working effectively and some interactions can create serious medical problems. Pharmacies can help identify potential interactions.
¡ Vitamin C – Doses greater than 1000 mg per day may be counterproductive in myeloma and can increase the risk of kidney damage.
Mental health
Your mental health is critical. Talk with a mental health professional if you feel anxious or depressed or if others are concerned about you. This is a normal response to cancer and most patients will need some help at one time or another. Support among peers may be helpful, and engaging with a myeloma support group can add to your support network. Visit support.myeloma.org or email sgteam@myeloma.org for help with finding an in-person or virtual group.
Physical activity
Check with your doctor to clarify what type of physical activity is appropriate for you. Usually, some physical activity can be planned, such as walking
or swimming, flexibility and strength exercises, and/or a personalized yoga program.
Your immune system
In myeloma, the patient’s immune system is compromised both by the disease and by its treatments. It is important for patients to remain current with their vaccinations, and to discuss this with their doctors. Wash your hands frequently, and be sure to get regular sleep!
Response or remission
Response and remission are interchangeable terms to describe the complete or partial disappearance of the signs and symptoms of myeloma. Remission is not a cure. It is generally considered to be at least a 50% improvement. The depth of response to myeloma treatment is classified as follows:
¡ Stringent complete response (sCR) is CR as defined below, plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.
¡ Complete response (CR) is negative immunofixation on serum (blood) and urine, and disappearance of any soft tissue plasmacytomas, and ≤ 5% plasma cells in bone marrow.
¡ Very good partial response (VGPR) is serum M-protein and urine M-protein detectable by immunofixation but not on electrophoresis, or ≥ 90% reduction in serum M-protein, plus urine M-protein < 100 mg per 24 hours.
¡ Partial response (PR) is a ≥ 50% reduction in M-protein, and reduction in 24-hour urinary M-protein by ≥ 90% (or to < 200 mg per 24 hours).
¡ Minimal response (MR) is a 25%–49% reduction of serum M-protein and reduction in 24-h urine M-protein by 50%–89% and, if present at baseline, a reduction in the size of plasmacytomas is also required.
The efficacy of current myeloma therapies is now assessed in terms of minimal residual disease (MRD) and MRD-negative status. MRD-negative means that not even 1 myeloma cell is found in 100,000 or 1,000,000 sampled bone marrow plasma cells (depending on the test used). MRD means that even after CR or sCR has been attained, a patient may still have myeloma cells remaining that can be verified with bone marrow testing –see Table 5.
It is important to note 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 determine 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.”
Table 5. IMWG criteria for response assessment including criteria for MRD
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 10 5 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 10 5 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
Maintenance therapy
Maintenance therapy prolongs remission after the patient has achieved maximum response to treatment. The benefit of continuous therapy until disease progression has been demonstrated to improve survival, but emerging evidence indicates that it may be possible to receive maintenance therapy for a shorter time, depending on the patient’s response to treatment.
The choice of maintenance therapy usually depends on the patient’s depth of response and if the patient has high-risk disease. It is critical to promptly report any side effects from maintenance therapy to the treating doctor so that the therapy can be adjusted.
Relapsing myeloma
Unfortunately, despite great advances with frontline therapies that produce deeper and more durable remissions, nearly all myeloma will relapse. 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 this treatment ended. In fact, there can be multiple periods of response and remission following treatment with consecutive lines of therapy.
Fortunately, a growing number of effective FDA-approved protocols has significantly expanded treatment options for relapsing patients.
Relapse is a key time to discuss with a myeloma specialist the overall strategy that is most appropriate for you and your myeloma. 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 you were 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.
Important terms to know include the following:
¡ Progression-free survival (PFS) is the length of time during and after the treatment that a patient lives with myeloma but the disease does not get worse. Most patients with myeloma have multiple remissions and relapses.
¡ Time-to-progression (TTP) is the time from start of treatment until myeloma relapses.
¡ Progressive disease is myeloma that is becoming worse or relapsing, defined as an increase of ≥ 25% from the lowest confirmed response value in the M-protein level and/or new evidence of myeloma.
Duration and depth of initial therapy
After achieving their first remission, myeloma patients experience their first relapse at variable intervals. The duration and depth of a patient’s response to frontline therapy is often predictive of long-term efficacy in managing myeloma, and helps guide the selection of the next course of treatment. Patients who achieve MRD-negativity status tend to have better PFS.
Biochemical relapse
Biochemical relapse means there is disease progression based on increase in M-protein levels, but no myeloma-related symptoms of 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 in cases where there is an abnormal ratio by 2 measurements taken 2 months apart: M-spike shows an absolute rise of 0.5 gm/dL or the light chains measured by sFLC show an increase of 10mg/dL or more.
Clinical relapse
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 there is any evidence of worsening CRAB criteria.
Relapse 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 at this time. 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.
Sequence of regimens after relapse
There is no ideal sequence of treatment regimens for a relapsing patient. Primarily, treatment options depend on the drugs to which the patient is no longer responsive. However, given the many new and emerging therapies, many patients have unexplored treatment options, including in the context of clinical trials.
Refractory myeloma
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.
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 late-stage relapse and with refractory disease, attaining stable disease can have clinical benefits for the patient. This is another key time to discuss with your doctor the risks and benefits of clinical trial participation, which may offer access to new drugs and new therapies not yet approved by the FDA.
Clinical trials
A clinical trial is a medical research study with people who volunteer to test scientific approaches to a new treatment or a new combination therapy. Each clinical trial is designed to find better ways to prevent, detect, diagnose, or treat a disease or a disorder and to answer scientific questions.
For patients with myeloma, clinical trials are part of normal care that can offer earlier access to new drugs and new therapies. According to the FDA, White individuals comprise over 70% of clinical trial participants even though almost 40% of the U.S. population is comprised of racial and ethnic minorities. Lack of diversity in myeloma clinical trials limits the development of effective and safe treatments for all patients.
If you wish to explore participating in a clinical trial, be sure to discuss with your myeloma doctor all the potential risks and benefits that may apply to your particular case. For more information about what’s involved in study participation, read the IMF’s publication Understanding Clinical Trials in Myeloma.
The IMF has partnered with SparkCures to help myeloma patients discover and explore clinical trials across the U.S. that best match their needs. To identify a clinical trial personalized to your preferences, visit myeloma.org/sparkcures or contact the IMF InfoLine.
The clinicaltrials.gov online U.S. government database of clinical trials also provides information about research studies. However, the government does not review the safety and science of all the studies submitted to this website.
IMF International Myeloma Working Group
The IMWG is one of the most prestigious international organizations for myeloma researchers. IMWG members conduct collaborative basic, clinical, and translational research to improve outcomes for patients with myeloma while providing scientifically validated, critically appraised consensus guidelines. The work of the IMWG has resulted in a greater understanding of myeloma and its treatments.
Since 2003, the IMWG has published about 70 consensus guidelines in premier medical journals, and this has had a profound impact on the care of patients with myeloma around the world. If you have an
interest in learning about myeloma from materials written for medical professionals, many of these papers are available through the IMF website at myeloma.org/imwg-publications.
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 a good quality of life through effective treatment, you must play an active role in your own medical care. We encourage you to visit myeloma.org for more information and to join the Myeloma Knowledge Platform at myprofile.myeloma.org.
To receive the most up-to-date information about myeloma in a caring and compassionate manner, call the IMF InfoLine at 1.818.487.7455, email InfoLine@myeloma.org, or schedule a time to talk with an IMF InfoLine Coordinator at mmsm.link/infoline.
To get answers to your questions without having to wait, ask Myelo® anytime 24/7 at myeloma.org. This generative AI assistant is designed to help you find the right resources.
Use the hyperlinks and web addresses included in this publication for quick access to resources from the IMF. Sign up at subscribe.myeloma.org for our quarterly journal Myeloma Today and weekly e-newsletter Myeloma Minute, as well as alerts about IMF news, events, and actions.
The International Myeloma Foundation (IMF) is the global leader in myeloma. Our mission is to improve the quality of life of myeloma patients while working toward prevention and a cure. Since 1990, the IMF has been serving the myeloma community through the following four pillars:
RESEARCH At the IMF, finding a cure for myeloma is our top priority. The IMF Scientific Advisory Board (SAB) of leading myeloma experts identifies key opportunities to drive research forward. The IMF Black Swan Research Initiative® (BSRI®) is pushing the boundaries with early screening for a precursor condition of myeloma as well as cure-focused myeloma clinical trials. The IMF International Myeloma Working Group (IMWG) provides trusted guidelines for diagnosing, treating, and managing myeloma. We also fund innovative research through the IMF Brian D. Novis Research Grants.
EDUCATION Myeloma is a complex and unique journey for each patient. The IMF offers hundreds of videos and free publications in multiple languages to inform and empower patients and care partners to navigate their myeloma journey. All IMF seminars, webinars, and workshops are free-of-charge and designed to directly connect the patient community with expert myeloma clinicians. The IMF Nurse Leadership Board (NLB) provides recommendations for the management of myeloma. The IMF M-Power Project works to break down barriers and ensure health equity in underserved populations.
SUPPORT Studies show that social support can greatly improve the quality of life of people with cancer. The IMF offers more than 160 myeloma support groups across North America, including specialized groups for Spanish-speakers, people with smoldering myeloma, care partners of patients with myeloma, and patients who do not have care partners. The IMF InfoLine answers myeloma-related questions. Myelo®, the IMF’s generative AI assistant, is available 24/7 to help you find the right resources.
ADVOCACY In the U.S., the IMF Advocacy team represents your interests at the federal and state levels. Internationally, the IMF Global Myeloma Action Network (GMAN) works to improve patient access to treatments.
