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Multiple Myeloma

NORD is very grateful to Morie A. Gertz, MD, Hematology and Internal Medicine, Mayo Clinic, for assistance in the preparation of this report.

Synonyms of Multiple Myeloma

  • Kahler disease
  • myelomatosis
  • plasma cell myeloma

Disorder Subdivisions

  • extramedullary plasmacytoma
  • nonsecretory myeloma
  • osteosclerotic myeloma
  • plasma cell leukemia
  • smoldering myeloma
  • solitary plasmacytoma of bone

General Discussion

Multiple myeloma is a rare form of cancer (1% of malignancy) characterized by excessive production (proliferation) and improper function of certain cells (plasma cells) found in the bone marrow. Plasma cells, which are a type of white blood cell, are produced in the bone marrow and normally reside there. Excessive plasma cells may eventually mass together to form a tumor or tumors in various sites of the body, especially the bone marrow. If only a single tumor is present, the term solitary plasmacytoma is used. When multiple tumors are present, the term multiple myeloma is used. Plasma cells are a key component of the immune system and secrete a substance known as immunoglobulin proteins (M-proteins), a type of antibody. Antibodies are special proteins that the body produces to combat invading microorganisms, toxins, or other foreign substances. Overproduction of plasma cells in affected individuals results in abnormally high levels of these proteins within the body, referred to as M proteins

Major symptoms of multiple myeloma may include bone pain, especially in the back and the ribs; low levels of circulating red blood cells (anemia) resulting in weakness, fatigue, and lack of color (pallor); and kidney (renal) abnormalities. In some cases, affected individuals are more susceptible to bacterial infections such as pneumonia. The cause of multiple myeloma is unknown.


The specific symptoms, age of onset, and rate of progression of multiple myeloma varies from case to case. Some affected individuals will not exhibit any symptoms (asymptomatic). Multiple myeloma may progress to cause life-threatening complications. It is important to note that affected individuals will not have all the symptoms listed below.

The most common symptom associated with multiple myeloma is bone pain, usually of the lower back or ribs. In most cases, movement worsens the pain, which may be mild, moderate or severe. Affected individuals are usually more susceptible to fractures than the general population and may experience repeated fractures of affected bones. The bones of the spine may become involved, potentially collapsing and resulting in spinal cord compression. Compression of the spinal cord results in pain, weakness and numbness in the arms and legs.

Another possible sign of multiple myeloma is an elevated level of calcium in the blood, a condition called hypercalcemia. This occurs because damage to bones often results in the release of calcium into the bloodstream. Abnormally high levels of calcium may result in nausea, lack of appetite, fatigue, abdominal pain, muscle pain and weakness, excessive thirst, and/or confusion.

Overproduction of plasma cells may also hinder the production and decrease the effectiveness of other cells of the body resulting in a variety of symptoms. Affected individuals may experience low levels of circulating red blood cells (anemia) resulting in weakness, fatigue, dizziness, shortness of breath, and lack of color (pallor). Affected individuals may also experience low levels of cells that assist in clotting (platelets), a condition known as thrombocytopenia. Symptoms associated with thrombocytopenia include abnormal bleeding episodes that often result in purplish discoloration of the skin resulting from bleeding (hemorrhaging) of small blood vessels near the surface of the skin (purpura). Affected individuals may rarely experience repeated nosebleeds (epistaxis).

Affected individuals may also experience low levels or reduced effectiveness of white blood cells, which weakens the immune system and results in affected individuals becoming more susceptible than the general population to developing recurrent bacterial infections. The most common infection is pneumonia. In some cases, recurrent infections may be the first apparent symptom of multiple myeloma.

Individuals with multiple myeloma may also develop kidney abnormalities. In some cases, hypercalcemia may cause kidney damage. In some cases, abnormal proteins found in the blood or urine (M-proteins), which are produced by myeloma cells, may cause kidney damage (myeloma kidney). Kidney abnormalities may develop slowly or rapidly, and may eventually progress to cause kidney (renal) failure.

In rare cases, individuals with multiple myeloma may have an abnormally large liver (hepatomegaly) or spleen (splenomegaly). In rare cases, multiple myeloma may occur in association with other disorders. The three most common disorders that may occur in association with multiple myeloma include hyperviscosity syndrome, cryoglobulinemia, or amyloidosis.

Hyperviscosity syndrome is characterized by the blood becoming abnormally thick and sticky due to the abnormal accumulation of M-proteins in the blood. As a result blood flow is slowed. Hyperviscosity syndrome may cause headaches, fatigue, frequent bruising, gastrointestinal bleeding, and vision abnormalities such as disease of the retina (retinopathy).

Cryoglobulinemia is a rare disorder that occurs due to the accumulation of abnormal proteins (cryoglobulins) in the bloodstream. These proteins thicken or gel on exposure to cold. In some cases there are no symptoms. In others a variety of symptoms may develop. The most common symptoms are joint pain (arthralgia), pain and numbness in the fingers and toes in response to cold (Raynaud's phenomenon), weakness, and purpura.

Amyloidosis is a rare disorder characterized by the abnormal accumulation of a fibrous protein (amyloidosis) in tissues of the body. The excessive accumulation of amyloid causes an affected organ to malfunction. (For more information on this disorder, see the Related Disorders section below.)


The exact cause of multiple myeloma is not known. Symptoms occur as a result of a process that is initiated by the abnormal multiplication of plasma cells in bone marrow. Scientists suspect there may be a variety of causes that may include environmental factors (e.g., the effects of exposure to radiation), genetic abnormalities, and/or additional factors that may play varying contributing roles.

One factor of interest to researchers is that many myeloma cells have been found to be missing all or part of chromosome 13. Also, the development of multiple myeloma is related in virtually all cases to a condition called monoclonal gammopathy of undetermined significance or MGUS (see Related Disorders section). The cause of MGUS is not known.

The specific symptoms of multiple myeloma result from excessive and unnecessary growth (neoplastic proliferation) of plasma cells.

Affected Populations

Multiple myeloma is a rare cancer that is slightly more common in males than females. In 2012, more than 21,700 individuals in the United States were diagnosed with this disease. It is believed that approximately 100,000 Americans currently have the disease.

According to reports in the medical literature, multiple myeloma accounts for approximately one percent of all malignancies in Caucasians and about two percent of all malignancies in individuals of African descent. It accounts for 10 percent of all hematological malignancies in the United States. The yearly incidence rate is estimated to be approximately four persons out of 100,000.

Multiple myeloma usually becomes apparent between the fourth and seventh decades of life, with a median age of 68 years at diagnosis. The occurrence of the disease before the age of 40 is rare.

Related Disorders

Symptoms of the following disorders can be similar to those of multiple myeloma. Comparisons may be useful for a differential diagnosis:

Waldenstrom macroglobulinemia is a lymph and blood cell disorder. Abnormally large quantities of homogeneous protein molecules are present in the blood. The disorder may run in families and occurs after the sixth decade. An enlarged spleen and liver with abnormalities of the lymph glands are the most frequent symptoms. Weakness, anemia, fatigue and excessive bleeding, especially from the nose and mouth, also occur. (For more information on this disorder, choose "Waldenstrom" as your search term in the Rare Disease Database.)

Heavy chain diseases are characterized by the presence of too many plasma cells or certain white blood cells (lymphocytes) that resemble plasma cells in the bone marrow and lymph nodes. This condition includes gamma, alpha and Mu heavy chain disease, which are all disorders of the proliferative type. Gamma heavy chain disease is characterized by anemia. The liver, spleen and lymph nodes are enlarged. Alpha heavy chain disease occurs most often in men of Mediterranean ancestry. It involves the digestive tract with severe malabsorption of nutrients, loss of weight, diarrhea, and loss of fat (steatorrhea). Symptoms are most often progressive. Mu heavy chain disease is characterized by a form of chronic lymphocytic leukemia or tumors of the lymph gland. Analysis of the blood serum usually reveals excessively low levels of antibodies in the blood (hypogammaglobulinemia).

Monoclonal gammopathy of undetermined significance (MGUS) is a condition characterized by the presence of M-proteins in the blood. There may be low levels of M-proteins in the urine. Individuals with MGUS do not have the physical symptoms associated with multiple myeloma (e.g., anemia, bony lesions, kidney abnormalities). In some cases, individuals with MGUS eventually develop a malignant disorder such as multiple myeloma, Waldenstrom's macroglobulinemia, or amyloidosis.

The term amyloidosis includes a group of disorders caused by abnormal folding, clumping, (aggregation) and/or accumulation of particular proteins (amyloids, fibrous proteins and their precursors) outside of the cell (extracellular), but within the tissues of various organs of the body. The accumulated amyloid causes the progressive malfunction of the affected organ. Normally, proteins are broken down at about the same rate as they are produced, however, these unusually stable proteins are deposited more rapidly than they can be broken down. The accumulation may be localized, or systemic. The most widely used classification of the amyloidoses is based on the biochemical nature of the fiber-like protein structures (fibrils) and on the nature of the precursor proteins that give rise to the amyloids. (See Disorder subdivisions above.) The different amyloidoses are named by combining the upper case A (for amyloid) with an abbreviation of the name of the protein that makes up the fibril. There are at least twenty (20) different types of fibrils that make up the human amyloidoses, and each is responsible for a unique clinical presentation. Older discussions of amyloidosis refer often to "primary amyloidosis" or to "myeloma-associated amyloidosis" the fibril protein of each of which is an immunoglobulin light chain peptide or fragment. The newer classification labels both of these as "light chain amyloidosis" or AL. The Light chain amyloidosis (AL) form of the disorder occurs most often, but not always, in association with an increased number of plasma cells in the bone marrow. AL affects the kidney, heart, intestinal tract, liver and/or spleen. Kidney or cardiac involvement may result in renal or congestive heart failure, respectively.

The following disorders may be considered variants of multiple myeloma:

Smoldering multiple myeloma (SMM) is characterized by abnormally high levels of atypical plasma cells in the bone marrow without evidence of symptomatic disease. Many affected individuals exhibit M-proteins in the urine and blood but have no other evidence of the symptoms of multiple myeloma such as anemia, bone lesions or kidney failure. Individuals with smoldering multiple myeloma may eventually develop multiple myeloma.

Plasma cell leukemia is characterized by the presence of excessive amounts of plasma cells in the blood.

Non-secretory myeloma exists when an individual with multiple myeloma does not produce M-protein in either the urine or blood serum. Individuals with non-secretory myeloma make up only one percent of individuals with myeloma.

Osteosclerotic myeloma is a variant of multiple myeloma. Major symptoms may include weakness; numbness in the legs, skin changes, hormonal abnormalities, and lung problems. In osteosclerotic myeloma, there is an association with osteosclerosis, a condition marked by hardening and abnormal density of bone. A common symptom of osteosclerotic myeloma is peripheral neuropathy. The exact cause of osteosclerotic myeloma is not known.

Solitary plasmacytoma of bone is characterized by only one plasma cell tumor (plasmacytoma) of the bone. Diagnosis relies on cell examination, and no evidence of multiple myeloma in the bone marrow.

Extramedullary plasmacytoma occurs when plasma cell tumors arise outside the bone marrow. The upper respiratory tract, which includes the nasal cavity and sinuses, nasopharynx, and larynx, is the most frequent site of involvement. However, extramedullary plasmacytomas have been found in virtually every organ of the body.

Standard Therapies

A diagnosis of multiple myeloma is made based upon a thorough clinical evaluation, a detailed patient history, and a variety of specialized tests. Such tests may include removal and microscopic examination of small samples of bone marrow (biopsy or aspiration), blood tests to detect low levels of red and white blood cells, and various x-ray techniques including magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) scanning that may reveal characteristic changes to bones. A test that uses electric currents to sort proteins in the blood or urine (electrophoresis) may be used to detect elevated levels of M-proteins.

The diagnosis and therapeutic management of multiple myeloma may require the coordinated efforts of a team of medical professionals, such as physicians who specialize in the diagnosis and treatment of cancer (medical oncologists), disorders of the blood and blood-forming tissues (hematologists), or the use of radiation to treat cancers (radiation oncologists); oncology nurses; surgeons; dietitians; and/or other professionals.

Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease stage; tumor size; the presence or absence of certain symptoms; individual's age and general health; and/or other elements. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.

In some cases, affected individuals may have a slow developing form of multiple myeloma that progresses over many years, often without symptoms (asymptomatic). Such individuals, and individuals with similar conditions like smoldering multiple myeloma and MGUS, may not require treatment. However, these individuals should be routinely monitored so that treatment can begin if symptoms appear.

The treatment of multiple myeloma usually involves chemotherapy to reduce the numbers of abnormal plasma cells, drugs to help fight infection (e.g., antibiotics), and medications to reduce pain (analgesic drugs). Additional treatment may include the use of high energy x-rays (radiation therapy) to destroy cancer cells and reduce bone masses that may develop. The use of new biologic drugs may also be recommended. If affected individuals experience involvement of the kidneys, fluids may need to be administered to avoid dehydration.

The following link provides information from the National Cancer Institute about medications that have been approved by the U.S. Food and Drug Administration (FDA) to treat multiple myeloma:

Stem-cell transplantation along with high-dose chemotherapy is regularly used for the treatment of multiple myeloma. Stem cells, which reside in the bone marrow, function as "parent" cells, undergoing a series of divisions that result in the formation of all the different types of blood cells (e.g., red blood cell, platelets, etc.).

Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials for multiple myeloma is posted on the Internet at All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (800) 411-1010

For information about clinical trials sponsored by private sources, contact:

For information about clinical trials conducted in Europe, contact:

Recombinant erythropoietin may be used as a treatment for anemia in some individuals with multiple myeloma. Recombinant erythropoietin is an artificial (synthetic) version of a natural hormone that stimulates the growth of red blood cells.

Researchers are studying the drug, denosumab (AMG 162) for the treatment of individuals with multiple myeloma. Denosumab suppresses bone turnover, a normal process in which bone gradually breaks down (bone resorption) and then reforms. A phase I clinical trial of individuals with multiple myeloma demonstrated rapid suppression of bone turnover. Further clinical trials are ongoing. More research is necessary to determine the long-term safety and effectiveness of this potential treatment for multiple myeloma.

Results from a multicenter phase III clinical study suggest that bortezomib plus melphalan and prednisone is effective for untreated elderly individuals with multiple myeloma. Bortezomib plus melphalan and prednisone was significantly superior to melphalan and prednisone. More research is necessary to determine the long-term safety and effectiveness of this treatment for elderly untreated individuals with multiple myeloma.

Contact for additional information about Multiple Myeloma:

Morie A. Gertz, MD
Hematology and Internal Medicine
Mayo Clinic
200 First Street S.W.
Rochester, MN 55905

Multiple Myeloma Resources

NORD offers an online community for this rare disease. RareConnect was created by EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders) to provide a safe space where individuals and families affected by rare diseases can connect with each other, share vital experiences, and find helpful information and resources. You can view these international, rare disease communities at

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at

Other Organizations:


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Kyle RA. Diagnostic challenges and standard therapy. Semin Hematol. 2000;38:11-14.

Kneller A, et al. Therapy with thalidomide in refractory multiple myeloma patients - the revival of an old drug. Br J Haematol. 2000;108:391-93.

Kyle RA, et al. Monoclonal gammopathy of undetermined significance. Hematol Oncol Clin North Am. 1999;13:1181-202.

Brigden ML. The search for meaning in monoclonal protein. Is it multiple myeloma or monoclonal gammopathy of undetermined significance? Postgrad Med. 1999;106:135-42.

Singhal S, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999;341:1565-71.

Attal M, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Eng J Med. 1996;335:91-97.

Berenson JR, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. N Eng J Med. 1996;334:488-93.

Wahlin A, et al. Effects of plasmapheresis on the plasma concentration of proteins used to monitor the disease process in multiple myeloma. Acta Med Scand. 1988;223:263-67.

Cooper MR, et al. Interferons in the treatment of multiple myeloma. Cancer. 1987;59:594-600.

Costanzi JJ, et al. The use of interferon in the treatment of multiple myeloma. Semin Oncol. 1987; 4:24-28.

Mayo Foundation for Medical Education and Research. Multiple Myeloma. Last Updated: August 16, 2011. Available at: Accessed:March 7, 2013.

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Report last updated: 2013/03/15 00:00:00 GMT+0

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