Understanding MGUS and Smoldering Multiple Myeloma
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 more than 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 .
You are not alone
The International Myeloma Foundation (IMF) is dedicated to providing information and support for patients with multiple myeloma (which we refer to simply as “myeloma”) and its precursor states, smoldering multiple myeloma (SMM, pronounced “ess-em-EM”) and monoclonal gammopathy of undetermined significance (MGUS, pronounced “EM-gus”). The IMF also serves the patient’s care partners, friends, and family members.
The IMF achieves this through a broad range of resources available on our website myeloma.org and through programs such as seminars, webinars, and workshops. The IMF InfoLine consistently provides the most up-to-date and accurate information to patients and their care partners in a caring and compassionate manner via 1.818.487.7455 or InfoLine@myeloma.org.
What you will learn from this booklet
MGUS and SMM are 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 to learn about your diagnosis. Clear communication is essential, as a diagnosis of either MGUS or SMM can cause anxiety.
Words in bold+blue type are explained in the “Terms and definitions” section at the end of this booklet. A more comprehensive glossary can be found in the IMF’s publication Understanding Myeloma Vocabulary located online at glossary.myeloma.org.
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 format at publications.myeloma.org.
Presence of myeloma defining events
Likelihood of progression ~1% per year ~10% per year not applicable
Treatment or observation observation only observation; treatment* treatment
*Treatment in the setting of a clinical trial or for high-risk patients likely to progress to active myeloma within 2 years.
1. Kyle et al. N Engl J Med. 2007;356:2582-2590.
2. International Myeloma Working Group. Br J Haematol. 2003;121:749-57.
3. Jagannath et al. Clin Lymphoma Myeloma Leuk. 2010;10:28-43.
4. Kyle et al. Curr Hematol Malig Rep. 2010;5:62-69.
5. Mateos et al. Blood 2009;114: abstract 614.
6. Durie and Salmon. Cancer 1975;36:842-854.
7. Durie et al. Leukemia 2006;20:1467-1473.
8. Rajkumar et al. Lancet Oncol. 2014;15:e538-e548.
MGUS
If it is suspected that you have monoclonal gammopathy of undetermined significance (MGUS) or if you are already diagnosed with MGUS, it is essential that you see an experienced hematologist, a doctor who specializes in the problems of blood and bone marrow.
MGUS occurs in 3% to 5% of the population in the United States. This rate is higher for those who are 50 years of age or older. MGUS is the earliest disease state associated with the subsequent development of myeloma. The risk of progression from MGUS to myeloma is discussed on page 7.
Types of MGUS
This booklet focuses on the plasma cell type of MGUS, which comprises 85% of all MGUS cases. MGUS can arise from either plasma cells or lymphoid cells, and these two types of MGUS are biologically different. The plasma cell type of MGUS can progress to become myeloma or a related disorder, including amyloidosis and light chain deposition disease (LCDD).
Plasma cells develop from a type of white blood cell (WBC) called B cells (B lymphocytes) and are a key part of the immune system. In the normal immune response, B cells mature into plasma cells in the bone marrow, where plasma cells produce antibodies that attach to antigens that enter the body.
How MGUS is diagnosed
Patients with MGUS have comparatively low levels of monoclonal protein (myeloma protein, M-protein) in the serum and/or urine. Bone marrow plasma cell levels are less than 10%. SLiM-CRAB criteria features are absent.
The laboratory tests used to measure the amount of M-protein are serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP). The amount of M-protein reflects the activity of abnormal plasma cells in the bone marrow. SPEP and/or UPEP should be repeated 3 to 6 months after MGUS is diagnosed. If your level of M-protein remains stable and there are no symptoms or other health changes, your doctor can extend the time between follow-up testing. Be sure to report any change in your health to your doctor.
Immunofixation electrophoresis (IFE) is an immunologic test of the serum or urine used to identify the exact heavy-chain and light-chain type of M-protein that is present. Your plasma cells can produce one of five classes (isotypes) of immunoglobulin (Ig). If you have the IgM type of M-protein, ask your doctor about a computed axial tomography (CAT or CT) of the abdomen to check for lymph node enlargement.
Normal SPEP result
Abnormal result with myeloma cells producing the M-protein, creating an M-spike in the beta-2 zone
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 by chemical bonds or it may be unbound and “free” to enter the bloodstream. Free light chains that circulate in the blood 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. For more information about free light chains and the test used to quantify them, read the IMF’s publication Understanding Freelite® and Hevylite® Tests.
Abnormal result with myeloma cells producing the M-protein, creating an M-spike in the gamma zone
If testing reveals evidence of myeloma or Waldenström macroglobulinemia (WM), you will be tested for levels of lactate dehydrogenase (LDH), beta-2 microglobulin (β2-microglobulin, β2M, or β2M), and C-reactive protein (CRP). If the test results are within normal ranges, you will be tested again in 6 months with SPEP and a complete blood count (CBC), and then annually for life or until any changes occur.
If MGUS is diagnosed or suspected, then additional testing may be performed at the discretion of your doctor. This includes bone marrow testing and imaging studies of bone (to rule out early bone disease). A bone marrow biopsy is always required if the patient has unexplained hypercalcemia, kidney dysfunction, anemia, bone lesions, or a suspicion of amyloid light-chain (AL) amyloidosis.
For a diagnosis of MGUS, all of the following criteria must be met:
1. Presence of M-protein in the serum < 3 g/dL,
2. Presence of monoclonal plasma cells in the bone marrow < 10%,
3. Absence of CRAB criteria.
For a diagnosis of light chain MGUS, all of the following criteria must be met:
1. Abnormal free light chain (FLC) ratio < 0.26 or > 1.65,
2. Level 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 immunoglobulin heavy chain expression on IFE,
4. Absence of CRAB criteria,
5. Presence of monoclonal plasma cells in the bone marrow < 10%,
6. Presence of M-protein in the urine based on a 24-hour collection < 500 mg.
Risk of progression from MGUS to myeloma
Progression from MGUS to active myeloma occurs at the low rate of only 1% per year. All patients who develop myeloma have previously had MGUS followed by smoldering multiple myeloma (SMM). Researchers are gaining a better understanding of the biologic events that take place when MGUS develops into myeloma, but it is not yet known what triggers the progression in some patients but not in others, or how to prevent progression. The IMF International Myeloma Working Group (IMWG) has established the following risk factors for MGUS progressing to myeloma:
1. M-protein level is more than 1.5 g/dL (can also be written as 15 g/L),
2. M-protein type is IgA or IgM, and
3. Abnormal FLC ratio of kappa to lambda FLCs.
Risk of progression from MGUS to active myeloma:
¡ Low-intermediate-risk MGUS has one of the risk factors.
¡ High-intermediate-risk MGUS has two of the risk factors.
¡ High-risk MGUS has all three of the risk factors.
CRAB Criteria
Myeloma-de ning events (MDE)
Bone marrow plasma cells ≥ 60%
Ratio of monoclonal to normal light chains ≥100
>1 focal lesion on MRI
Spanish Criteria
Mayo Criteria
MM Multiple Myeloma
Early Active Myeloma Ultra-High-Risk Smoldering Myeloma
HR SMM High-Risk Smoldering Multiple Myeloma
LR SMM Low-Risk Smoldering Multiple Myeloma
MGUS Monoclonal Gammopathy of Undetermined Signi cance
If you are diagnosed with intermediate-risk or high-risk MGUS during your baseline testing, you should also have a bone marrow aspiration and bone marrow biopsy. The same bone marrow sample that is obtained should also be used for cytogenetic studies. For more information about the tests used to identify and quantify M-protein, read the IMF’s publication
Understanding Your Test Results.
Management for MGUS
At this time, there is no treatment for MGUS. Monitoring MGUS as described above can determine if any progression is occurring and if any additional testing is required. The risk of progression is 1% per year, and the vast majority of MGUS patients are monitored without need for additional medical attention for many years.
The iStopMM screening study
Launched in November 2016, iStopMM® (Iceland Screens Treats or Prevents Multiple Myeloma) is the largest-ever population-based screening study for MGUS, SMM, and myeloma. The iStopMM study invited the approximately 140,000 residents of Iceland who are over age 40 to be screened for the presence of M-protein in the serum or urine.
More than half of the invited population volunteered to take part, and the iStopMM research team, led by Dr. Sigurður Kristinsson (University of Iceland, Reykjavík), is observing patterns of occurrence in order to better understand disease biology and to identify the genes that drive disease progression. Monitoring patients with MGUS for many years will
demonstrate which prognostic tests are most reliable and which patients may benefit from early intervention.
The iStopMM study has defined, for the first time, epidemiological and clinical characteristics of SMM. An important early finding was that the prevalence of SMM is higher than expected: 0.53% in persons 40 years or older, 0.67% in men and 0.39% in women, with the prevalence increasing with age. This finding enhances the potential value of screening in that early interventions can be offered with hopes of improved outcomes.
Collectively, the iStopMM study findings point to many new paradigms in the evaluation and management of M-protein disorders. This is the beginning of a new era in the study of early disease entities which can be precursors to myeloma.
The many diverse outcomes from the iStopMM study will benefit not only Iceland but the myeloma community around the world. iStopMM is supported by the IMF Black Swan Research Initiative® (BSRI®) and you can find up-to-date information on its dedicated webpage myeloma.org/black-swan-research-initiative/istopmm.
SMM
Smoldering multiple myeloma (SMM) is an asymptomatic (no signs or symptoms) precursor state of active myeloma, similar to MGUS but at a higher level of disease. The average risk of progression from SMM to myeloma is 10% per year. Unlike active myeloma, patients with SMM do not have CRAB criteria features indicating organ damage. Patients with SMM should be observed by a hematologist-oncologist at regular intervals.
Diagnostic criteria for SMM
For a diagnosis of SMM, both of the following 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%,
2. Absence of myeloma-defining events (MDE) or amyloidosis.
Myeloma-defining events (MDE) include the following:
¡ 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 magnetic resonance imaging (MRI) studies.
Of the 193 participants in the iStopMM study who were diagnosed with SMM, the median age was 70 years (range 44–92) and 60% were males. Using the 2/20/20 clinical risk stratification criteria for SMM, 126 (65%) patients were low-risk, 52 (27%) intermediate-risk, and 15 (8%) high-risk.
The 2/20/20 criteria published by Mayo Clinic in 2018 are based on the data for patients who had none, one, or two to three of the risk factors that were most associated with a short time to progression from SMM to active myeloma:
¡ Serum M-protein > 2 g/dL,
¡ Bone marrow plasma cell (BMPC) infiltration > 20%, and/or
¡ Ratio of involved-to-uninvolved serum FLC > 20.
SMM may be diagnosed in a patient who is being observed for MGUS, or detected when an individual seeks healthcare due to an unrelated condition, or in the course of a routine medical exam. Once SMM is diagnosed, current clinical guidelines recommend stratification to determine the risk of progression to myeloma, as well as lifelong monitoring for progression.
The current understanding of the biology and behavior of SMM enables doctors to avoid treating patients who do not need to be treated, but to intervene promptly if a patient is at a high risk of progression to myeloma. The doctor’s experience and judgment are crucial to differentiating MGUS from SMM and from active myeloma. A primary consultation or second opinion with a myeloma expert is highly recommended.
The diagnostic process includes SPEP, CBC, and measurement of calcium and creatinine values. Twenty-four-hour urine collection for electrophoresis and immunofixation should be performed at diagnosis and within 2 to 3 months after the initial recognition of SMM. A baseline bone marrow biopsy and skeletal survey must be performed. An MRI of the spine and pelvis are highly recommended because these sensitive studies are better able to predict for more rapid progression to active myeloma.
Skeletal X-rays are no longer the standard of care in the diagnostic process of SMM because they only pick up bone lesions after approximately 30% of the cancellous bone has been destroyed. Whole-body low-dose CT (WBLDCT) is now the standard of care to detect and document early bone disease. WBLDCT is the preferred baseline imaging study for newly diagnosed myeloma because it does not require the use of contrast agents and also uses much less radiation than conventional CT.
Monitoring of patients with SMM
Patients with SMM are monitored more frequently than patients with MGUS because the risk of progression to active myeloma is higher. If you have been diagnosed with SMM, you must be carefully evaluated by a hematologist-oncologist every 4 to 6 months for the first year. If your SMM remains stable after a year, the evaluation can be lengthened to every 6 to 12 months based on your SMM status and your doctor’s judgment.
Possible evolution of SMM to active myeloma
Research is ongoing to identify the risk factors for progressing from SMM to active myeloma but a system of precise criteria does not exist at this time.
In 2014, The Lancet published the IMWG updated criteria for the diagnosis of myeloma. SMM patients with 80% or greater risk of progression to myeloma within 2 years were defined as having early active myeloma. To help prevent the development of end-organ damage, a patient should be treated for myeloma if any of the myeloma-defining events (MDE) are present.
In 2018, Blood Cancer Journal published a statistical analysis of variables among patients with SMM at Mayo Clinic in Rochester, Minnesota. Further refinements to the 2/20/20 criteria were made with the addition of the following two high-risk factors:
¡ chromosomal abnormality +1q (a gain of chromosome 1q),
¡ chromosomal abnormality del13q (a deletion of chromosome 13q).
If one or both of these abnormalities are found by fluorescence in situ hybridization (FISH) testing of myeloma cells, the risk of disease progression is increased.
In 2020, Blood Cancer Journal published the IMWG risk stratification model for SMM that can be applied across the globe using easily available data. Dr. María-Victoria Mateos and colleagues assembled an international cohort of 1,996 patients with SMM who met the revised IMWG criteria. Patients with ≥ 80% risk of progression at 2 years were excluded because they are considered to have active myeloma by current definition.
Three independent factors were identified predicting high-risk SMM (HR SMM) progression to active myeloma at 2 years based on the 2/20/20 criteria. This translates into 3 categories with an increasing 2-year progression risk:
¡ 6% for low-risk patients with no risk factors,
¡ 18% for intermediate-risk patients who have 1 factor, and
¡ 44% for high-risk patients who have 2 or more factors).
Figure 4. Karyotype analysis of human chromosomes
5. Fluorescence in situ hybridization (FISH) of a myeloma cell
In addition, presence of chromosomal abnormalities t(4;14), t(14;16), +1q, and/or del13q allowed for further separation into the following 4 groups:
1. Low-risk SMM patients had no cytogenetic abnormalities. Low risk of progression to active myeloma.
2. Low intermediate-risk SMM patients with 1 cytogenetic abnormality had the progression risk at 2 years of 23%.
3. Intermediate-risk SMM patients with 2 cytogenetic abnormalities had the progression risk at 2 years of 46%.
4. High-risk SMM (HR SMM) patients with 3 or more cytogenetic abnormalities had the progression risk at 2 years of 63%.
Treatment for SMM
Typically, SMM is not treated. There are no standardized treatment options for patients with SMM.
Currently, there are a number of clinical trials investigating SMM, including studies launched with the support of the IMF Black Swan Research Initiative. 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 cancer and to answer scientific questions.
If you have SMM and are interested in taking part in a clinical trial, discuss your options with your doctor. You must have a clear understanding of your relative risk of progression to active myeloma and of the potential risks and benefits of treatment in your particular case, including the psychological aspects of treatment as opposed to observation.
Active myeloma
Myeloma is a cancer of the bone marrow plasma cells, white blood cells that make antibodies. Cancer is 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. Malignant plasma cells are called myeloma cells.
If your SMM is progressing to active myeloma, this is a key time to seek an opinion (or a second opinion) from a myeloma specialist. A local hematologist or oncologist might see a few myeloma patients or none at all. Myeloma specialists at large “high-volume” treatment centers and large academic institutions see hundreds of myeloma patients, conduct clinical trials with new drugs and new combination therapies, and develop the expertise needed to make appropriate decisions.
A diagnosis of active myeloma is made when the patient has 10% or more clonal plasma cells in bone marrow, plus at least one myeloma defining event (MDE). Myeloma is a highly individual disease. Often, it is slow-moving. Sometimes, it can be very aggressive. The urgency of treatment depends upon the exact problems faced by an individual patient. An experienced myeloma specialist can tailor a treatment approach best suited to your specific situation, as well as anticipate and prevent or mitigate treatmentrelated problems.
Many highly effective therapies are approved for the treatment of myeloma by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and by other regulatory agencies. New approvals are expanding treatment options and the rate of development of new drugs continues to accelerate.
Many patients with myeloma lead full and productive lives for years, even decades, after diagnosis. Survival and quality of life of myeloma patients are improving steadily. Learning about myeloma and understanding how it is treated can help patients and their loved ones reduce their anxiety, gain a sense of control, and make it easier to come to terms with the diagnosis.
If you have been diagnosed with active myeloma, we suggest that you read the IMF’s publication Patient Handbook for the Newly Diagnosed, which will help you to better understand this complex disease. We also recommend that you read the IMF’s publication Understanding Your Test Results, which discusses the tests that are used to diagnose, monitor, and assess myeloma status throughout its disease course.
Support groups for patients with myeloma, SMM, and MGUS
The IMF provides educational guidance to a network of more 150 myelomaspecific support groups in the U.S. that offer empowerment, empathy, and encouragement to patients and their care partners. Many groups meet in person and some meet on a virtual platform supported by the IMF.
In addition, there are specialty groups that serve patients with SMM or MGUS and their loved ones. “Smolder Bolder,” a support group for people living with SMM, holds regular meetings on a virtual platform and can be reached at smm@imfsupport.org.
Please visit support.myeloma.org or email sgteam@myeloma.org to find an in-person or virtual group that best serves your needs or to start a new support group with help from the IMF.
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 terms can be found in the IMF’s publication Understanding Myeloma Vocabulary located online at glossary.myeloma.org.
Amyloid light-chain (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. See “Amyloidosis.”
Amyloidosis: A group of systemic diseases characterized by the deposition of amyloid protein in various organs or tissues. AL amyloidosis is the one type of amyloidosis that is related to myeloma. See “Amyloid light-chain (AL) amyloidosis.”
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).”
Antigen: Any foreign substance that causes the immune system to produce natural antibodies. Examples of antigens include bacteria, viruses, parasites, fungi, and toxins.
B cells (B lymphocytes): White blood cells that are part of the natural immune system. Some B cells develop into plasma cells in the bone marrow and are the source of antibodies.
Beta-2 microglobulin (β2-microglobulin, β2M, or β2M): A small protein found in the blood. High levels occur in patients with active myeloma. Low or normal levels occur in patients with early myeloma and/or inactive disease. Approximately 10% of patients have myeloma that does not produce β2M. At the time of relapse, β2M can increase before there is any change in the myeloma protein level. Factors such as viral infection can sometimes produce elevated serum β2M levels.
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.
Bone marrow biopsy: The removal, by a hollow-bore needle, of a sample of tissue from the bone. The tissue cells are checked to see whether they are cancerous. If cancerous plasma cells are found, the pathologist estimates how much of the bone marrow is affected. Bone marrow biopsy is usually done at the same time as bone marrow aspiration.
C-reactive protein (CRP): A protein made in the liver that increases in amount when there is inflammation throughout the body.
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.”
Cancellous bone: Also known as trabecular bone; the light, porous bone enclosing numerous large spaces that give it a sponge-like appearance. Trabecular bone contains marrow and blood vessels.
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).
• Chromosomal 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–).
• Chromosomal 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).
Complete blood count (CBC): Many cases of MGUS, SMM, and myeloma are identified as the result of this routine blood test, which quantifies all the cells that make up the solid parts of blood. The CBC is usually performed as part of an annual medical exam, and it is also one of the tests needed for diagnosing and monitoring patients with myeloma.
Computed axial tomography (CAT or CT): Creates three-dimensional images of structures inside the body. In myeloma, used when X-rays are negative or for more detailed scanning of specific areas. Especially useful for detection or detailed evaluation of small areas of bone damage or nerve pressure.
CRAB criteria: An elevated level of Calcium in the blood, Renal (kidney) damage, Anemia or low red blood cell count, and Bone damage are criteria used to diagnose myeloma along with “Myeloma-defining event (MDE).”
Creatinine: A chemical compound normally excreted by the kidneys into the urine. If the kidneys are damaged, the serum level of creatinine builds up. The serum creatinine test is used to measure kidney function.
Cytogenetics: Laboratory testing that looks for missing, rearranged, or extra chromosomes. See “Chromosome.”
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.
Fluorescence in situ hybridization (FISH): A procedure that allows myeloma specialists to locate the positions of specific DNA sequences on chromosomes.
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.”
Immune system: A complex network of cells, tissues, organs, and the substances they make. The immune system helps the body defend itself by destroying infected and diseased cells and removing cellular debris, while protecting healthy cells.
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 immunoglobulin has a different function in the body. See “Antibody ” and “Antigen.”
• IgG, 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.
• IgM – This is a rare type of myeloma. IgM myeloma is not the same as Waldenström macroglobulinemia.
Lactate dehydrogenase (LDH): An energy-producing enzyme that is present in almost all of the tissues in the body. LDH levels in the bloodstream rise in response to cell damage. LDH may be used to monitor myeloma activity.
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.
• Diffuse lesion – A spread-out pattern of myeloma bone marrow involvement in an area of bone.
• Focal lesion – An abnormal area seen in the bone marrow on MRI or PET-CT study. In order to be considered a “myeloma-defining event,” there must be more than 1 focal lesion of at least 5mm in size.
• Lytic 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 deposition disease (LCDD): A rare type of monoclonal immunoglobulin deposition disease (MIDD) that is characterized by deposition of complete or partial monoclonal light chains in organs. LCDD usually affects the kidneys but can also affect other organs. The goal of treating LCDD is to slow damage to organs.
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.”
Magnetic resonance imaging (MRI): Diagnostic imaging that uses magnetic fields and radio waves to produce detailed 2D or 3D images of structures inside the body. MRI can reveal the presence and distribution of myeloma in the bone marrow when X-rays show no damage. MRI can reveal myeloma outside of bone. MRI gives fine resolution of soft tissues, especially encroachments on the spinal cord.
Median: The mean (middle) of two central numbers in a series of numbers. For example, “median progression-free survival (mPFS)” means that half the patients had remissions that were shorter and half the patients had remissions that were longer than the mPFS.
Monoclonal: A monoclone is a duplicate derived from a single cell. Myeloma cells are monoclonal, derived from 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 on the protein electrophoresis test. See “M-spike.”
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.”
Myeloma-defining event (MDE): The diagnosis of myeloma requires evidence of one or more MDE: CRAB criteria, 60% or more monoclonal plasma cells in the bone marrow, ratio of involved-to-uninvolved serum FLCs of 100 or higher, or more than 1 focal lesion in the bone marrow that is greater than 5 mm in size detected on MRI. See “CRAB criteria.”
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).
Serum: The colorless, liquid part of blood in which the blood cells are suspended.
SLiM-CRAB criteria: This acronym outlines myeloma-defining events (MDE) where patients have 10% or more plasma cells, plus one of the following features:
• S – Sixty percent (60%) plasma cells,
• Li – Light chains involved:uninvolved ratio of 100 or more,
• M – MRI imaging of more than 1 focal lesion in bone marrow,
• C – Calcium elevation due to myeloma,
• R – Renal (kidney) insufficiency due to myeloma,
• A – Anemia (low red blood cell count) due to myeloma,
• B – Bone disease attributable to myeloma.
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.
INTERACTIVE RESOURCES AT A GLANCE
Use the hyperlinks and web addresses included in this publication for quick access to resources from the IMF.
Contact the IMF InfoLine with your myeloma-related questions and concerns infoline.myeloma.org
about FDA-approved therapies for myeloma medications.myeloma.org
Diversity and inclusion are integral aspects of the myeloma community diversity.myeloma.org
IMF booklets, tip cards, guides, and periodicals –subscribe to stay in the know! publications.myeloma.org
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