Also Known As
Plasma Cell Myeloma
Plasma Cell Dyscrasia
Plasmacytoma
Plasmacytoma of Bone
Plasma Cell Neoplasm
Extraosseous Plasmacytoma
This article was last reviewed on
This article waslast modified on
November 27, 2017.
What is multiple myeloma?

Multiple myeloma is a cancer of plasma cells. Plasma cells develop from one type of white blood cell called B lymphocytes and are an important part of the immune system. Their primary function is to produce antibodies – targeted immunoglobulin proteins that help protect the body against infections. Normally, plasma cells are produced as needed. When the immune system is exposed to disease-causing bacteria and viruses (pathogens), some B cells become plasma cells and begin to produce antibodies. Plasma cells can be seen in bone marrow, lymphoid tissues (such as lymph nodes), and the respiratory tract, usually in low numbers. Photo source: NCI, Lydia Kibiuk

Sometimes, however, a plasma cell may become malignant. It begins to divide uncontrollably, generating numerous copies of itself (clones) that form tumors in the bone marrow and crowd out other types of normal cells. In time, these tumors interfere with normal cell production and erode the surrounding bone, producing soft spots and holes (lytic lesions). Depending on the number of tumors, this condition has different names:

  • Plasmacytoma—a single plasma cell tumor forms in the bone or elsewhere in the body
  • Multiple myeloma—more than one plasma cell tumor forms in the bone

Since the malignant cells are clones, derived from a single plasma cell, they all produce identical antibodies called abnormal Monoclonal immunoglobulins (M proteins), which are present in the blood and sometimes in the urine.

Normally, the body makes five different types of immunoglobulins – IgG, IgM, IgA, IgE and IgD. Each one has slightly different immune system functions. Each type of immunoglobulin is composed of four protein chains – two identical heavy (long) protein chains and two identical light (shorter) protein chains.

  • The heavy chains may consist of one of five different types that correspond with the type of immunoglobulin produced: gamma (IgG), mu (IgM), alpha (IgA), epsilon (IgE) and delta (IgD).
  • The light chains consist of one of two different types called kappa and lambda.

Within a plasma cell, two heavy chains of one type and two light chains of one type become attached to form one intact immunoglobulin molecule. Each particular plasma cell will produce only one type of immunoglobulin.

In people with multiple myeloma, the malignant plasma cells produce only one type of intact (whole) immunoglobulin in large amounts and/or produce an excess of only one of the light chains, or rarely heavy chain-only types. These identical immunoglobulins or light chains are also known as Monoclonal proteins or M proteins. Though the type of M protein produced by malignant cells may vary from one person to the next, within one particular person it is always the same since it is produced by identical or cloned plasma cells.

The type of myeloma a person has is often referred to by the type of M protein produced, whether an intact immunoglobulin or light chain.

  • Intact immunoglobulin—people are most likely to have IgG and IgA myelomas, with IgG types making up about 60% of myelomas and IgA types making up about 20% of myelomas. Cases of IgE and IgD are rarely reported. Some people who produce monoclonal IgM may have a related but different condition called Waldenström macroglobulinemia. (For more on this, see the American Cancer Society's webpage on this disorder and the International Waldenstrom's Macroglobulinemia Foundation site.)
  • Light chain—myeloma patients producing an abnormal amount of only light chains are in the minority. They comprise about 20% of cases. The M-proteins that they produce are called free light chains (Bence Jones) proteins. Surplus free light chains are released into the bloodstream and since they are relatively small molecules, they are filtered by the kidneys and released into the urine. Free light chains are typically found in small quantities in the blood and large quantities in the urine.

Risks
Multiple myeloma is relatively uncommon and comprises about 1% of cancers. The American Cancer Society estimates that about 30,000 new cases of multiple myeloma are diagnosed each year in the U.S. and that 12,500 people with multiple myeloma die.

The cause of multiple myeloma is not yet known. The risk of developing it increases with age, with the majority of cases being diagnosed in people at least 65 years old. While there are a few families who have a higher incidence of multiple myeloma, most people will not have any affected relatives. It is thought that the disease may be associated with a decrease in immune system function, occupational exposure to toxins and/or solvents, genetic factors, certain viruses, and radiation exposure.

 Monoclonal Gammopathy of Undetermined Significance (MGUS)
Sometimes people will produce small amounts of identical copies of the same immunoglobulin (also known as monoclonal gammopathy) but not have any of the signs, symptoms, or complications of multiple myeloma. This condition is referred to as monoclonal gammopathy of undetermined significance or MGUS. Often, this condition is only discovered when routine tests reveal abnormal amounts of protein in the blood. About 1% of these people per year progress to multiple myeloma or some other related disease, such as lymphoma. Generally, these people do not require any treatment, but they are closely monitored. Some of the tests used to diagnose and/or follow multiple myeloma are used to monitor people with MGUS.

Accordion Title
About Multiple Myeloma
  • Signs and Symptoms

    Many people with multiple myeloma show no symptoms for many years (so-called asymptomatic myeloma). Eventually, most develop some signs and symptoms of the disease. These may include:

    • Weakened bones and bone pain; as bones weaken, soft spots and fractures may develop.
    • Carpal tunnel syndrome is a common complication.
    • Destruction of the bone that frequently increases the level of calcium in the blood, leading to symptoms of hypercalcemia such as loss of appetite, nausea, thirst, fatigue, constipation, and confusion.
    • An increase in abnormal plasma cells that decreases the number of normal red blood cells, white blood cells, and platelets, often resulting in anemia, recurrent infections, and excessive bleeding and bruising.
    • Kidney disease may develop. Bence Jones proteins can affect the kidneys and may permanently damage them.
    • In some cases, an increase in the thickness (viscosity) of the blood may lead to headaches or problems with vision. Hyperviscosity syndrome results from the increased presence of serum immunoglobulin proteins or blood cells causing an abnormal "thickness" to the blood. This, in turn, may cause nervous system symptoms, vision impairment, and/or excessive bleeding from the gums or nosebleeds. Up to 10% of patients with multiple myeloma and 10%-30% of patients with Waldenstrom macroglobulinemia may show increased serum viscosity.
  • Tests and Staging

    The goals of testing for multiple myeloma are to diagnose the condition, determine its severity and spread, monitor its progress, detect complications as they arise, and monitor the effectiveness of treatment.

    There is no one single test that can diagnose multiple myeloma. Typically, the disease is diagnosed using a combination of a person's signs and symptoms, medical history, physical examination, laboratory tests, and/or imaging tests.

    Laboratory tests
    Multiple myeloma may first be detected during routine wellness testing. It may be suspected when a person has:


    Findings such as these may raise suspicions but are not diagnostic as similar results may be seen with a variety of other conditions. Rather, they indicate the need for further testing.

    Tests used as a follow-up to abnormal routine tests and to help diagnose the disease may include one or more of the following:

    • Protein and immunofixation electrophoresis. These tests are used to help diagnose and monitor multiple myeloma. Protein electrophoresis separates the proteins in a blood or urine sample into several groups based on their electrical charge and size. In most people with multiple myeloma, large amounts of an abnormal immunoglobulin protein (M-protein) may show up as a large peak on the electrophoresis scan, also known as an M spike. The amount of normal immunoglobulins in the sample may be visibly decreased as well. Usually, both a blood and a urine sample will be tested to detect free light chains and intact immunoglobulins. Immunofixation electrophoresis is done to identify the specific type of protein that is being produced by the malignant plasma cells. The amount of protein produced may vary throughout the course of the disease, but the type will remain the same.
    • Urine free light chains (Bence Jones protein). These can be detected in the urine of some people with multiple myeloma. The sample tested is usually a 24-hour urine (a collection of all urine voided over a 24-hour period) because the total amount of free light chains in 24 hours is related to the amount of tumor that is present. Either the kappa or lambda light chains (but not both in the same person) may be measured to help diagnose multiple myeloma and monitor the effectiveness of treatment.
    • Serum free light chains (SFLC). This test measures the amount of free light chains in the blood. Even in normal circumstances (and for unknown reasons), plasma cells produce an excess of light chains compared to heavy chains, and there is usually a small amount of light chains that do not become incorporated into intact immunoglobulins. These remain as free light chains and are released into the bloodstream. Most people with multiple myeloma produce increased amounts of either kappa or lambda free light chains, which can be measured in blood. Consequently, the ratio of kappa to lambda light chains is abnormal and is a sensitive indicator for this disease. This test is used to monitor progression and/or treatment.
    • Quantitative immunoglobulins. Each of these tests measures amounts of a different type of immunoglobulin, or antibody, in the blood. The multiple myeloma protein may be an IgG, IgA or, rarely, an IgD or IgE immunoglobulin. People with a monoclonal IgM immunoglobulin may have a related but different disease (Waldenstrom macroglobulinemia). Tests for IgG, IgA, and IgM may be ordered to help diagnose multiple myeloma and to monitor the course of the disease and its effect on the production of normal immunoglobulins. Note that the test does not differentiate abnormal immunoglobulin produced by myeloma cells and the non-tumor immunoglobulin of the same type produced by normal plasma cells.
    • Serum immunoglobulin heavy chain/light chain. These tests can identify separately the different light chain types of each immunoglobulin class, including IgG-kappa, IgG-lambda, IgA-kappa, IgA-lambda, IgM-kappa, and IgM-lambda. The molecules are then measured in pairs (e.g., IgG-kappa / IgG-lambda) to calculate ratios of involved monoclonal immunoglobulin to background uninvolved immunoglobulin concentrations. The tests can be used to monitor people with multiple myeloma.
    • Bone marrow aspiration and biopsy. 
Multiple myeloma is a disease of the bone marrow. People usually require a bone marrow evaluation to confirm the diagnosis, evaluate how many malignant plasma cells are present in the marrow, and determine to what degree they have affected the production of normal white blood cells, red blood cells, and platelets.
    • Cytogenetic analysis. In these tests, which include karyotyping and florescence in situ hybridization (FISH), cells are examined under a microscope to look for abnormal chromosomes. Abnormalities like chromosome translocations (mismatched parts) or deletions are sometimes associated with multiple myeloma. Finding these abnormalities can provide information about an individual's prognosis.


    Other laboratory tests
    Other tests that may be done as part of an initial diagnostic workup, to monitor the progress of the disease, and to help detect and address complications include:

    • Comprehensive metabolic panel (CMP), a group of tests used to evaluate kidney and other organ function, electrolyte status, and to determine calcium, albumin, and total protein levels
    • Complete blood count (CBC), counts and evaluates white blood cells, red blood cells, and platelets and determines the extent of anemia (measures hemoglobin)
    • Uric acid levels may be elevated as a complication of multiple myeloma.
    • Beta-2 microglobulin, a protein on the cell surface of myeloma and other cells; increased levels may indicate a poorer prognosis; this test may be used to help stage the disease.
    • Serum viscosity, a measure of how "thick" the fluid portion of the blood is; when levels of the abnormal protein become very high, serum viscosity may increase and cause symptoms.


    Non-laboratory tests

    • X-ray, ordered to help diagnose, stage, and monitor; may detect holes in bones, extent of bone damage, and the number and size of tumors in the bones.
    • MRI (magnetic resonance imaging), may be more sensitive than X-ray for evaluating bone destruction.
    • CT (computed tomography)/PET (positron emission tomography), may be used to look for bone tumors when an x-ray result is negative but an individual still has bone pain.


    Staging
    Staging helps to determine a person's prognosis and allows the person and their healthcare practitioner to develop an individualized monitoring and treatment plan. Staging evaluates the:

    • Amount of abnormal immunoglobulin being produced
    • Amount of calcium in the blood
    • Degree and severity of bone damage
    • Extent of anemia

    There are different staging systems available to assess the amount of tumor tissue present (tumor burden) and organ dysfunction. Some test results, such as blood levels of beta-2 microglobulin and albumin, are especially important in myeloma staging.

  • Treatment

    At this time, multiple myeloma is not considered curable, although current treatments may produce a complete remission (disappearance but not cure of the disease) in some people. The goals of treatment are to relieve pain and other symptoms, to decrease the amount of cancer present or eliminate it, to slow the progress of the disease, and/or to detect and minimize complications as they occur.

    People who do not have significant symptoms are monitored but may not receive any treatment. Healthcare practitioners generally recommend that people with multiple myeloma stay as active as possible to help preserve the calcium in their bones and drink plenty of fluids to help with kidney function.

    Complications such as infections, anemia, and bleeding should be promptly addressed with measures such as antibiotics and, when necessary, blood transfusions. Other supportive treatments may include injections of immunoglobulins to help fight infections and plasmapheresis to remove excess M protein from the blood. Plasmapheresis helps reduce the thickness (viscosity) of the blood.

    If treatment is indicated, a combination of the following may be used:

    • Bisphosphonates—drugs that slow the weakening of bones
    • Chemotherapy—drugs used to control or destroy cancerous plasma cells
    • Targeted therapy—drugs that target the specific cancer's cells, genes or proteins
    • Radiation therapy—may be used to treat areas of bone that has not responded to chemotherapy
    • Stem cell transplantation—this procedure involves killing cells within the bone marrow, including the myeloma cells, and then giving the patient healthy stem cells


    For additional details about treatment, see the National Cancer Institute's webpage on Treatment Options for Plasma Cell Neoplasms.

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