Multiple myeloma is a cancer of plasma cells. Plasma cells develop from a type of white blood cell called B lymphocytes. Normal plasma cells produce antibodies that help the body to fight infections. Multiple myeloma cells grow uncontrollably in the bone marrow and occasionally in other parts of the body.
Multiple myeloma most often occurs in people 60 or older. Although its cause is not certain, the increased occurrence among close relatives indicates that heredity plays a role. Exposure to radiation is a possible cause, as is exposure to benzene and other chemicals. Infection with a type of herpes virus may play a role.
In multiple myeloma, the overabundance of cancerous cells in the bone marrow suppresses development of normal white blood cells, red blood cells, and platelets. In addition, the cancerous cells almost always produce a large amount of a single type of antibody accompanied by a markedly reduced amount of all other types of normal antibodies.
Often, collections of cancerous plasma cells develop into tumors that destroy bone tissue, most commonly in the pelvic bones, spine, ribs, and skull. Infrequently, these tumors develop in areas other than bone, such as the lungs, liver, and kidneys.
Because plasma cell tumors often invade bone, pain may occur, often in the back, ribs, and hips. Plasma cell tumors cause loss of bone density (osteoporosis), which weakens bones, making fractures more likely. Calcium is released from the bones, which may result in abnormally high levels of calcium in the blood. High calcium levels can affect the heart, kidneys, and brain, possibly causing constipation, increased frequency of urination, weakness, and confusion.
The reduced production of red blood cells often leads to anemia, which causes fatigue and weakness and may lead to heart problems. The reduced production of white blood cells leads to repeated infections, which may cause fever and chills. The reduced production of platelets impairs the blood's ability to clot and results in easy bruising or bleeding.
Pieces of monoclonal antibodies, known as light chains, frequently end up in the kidneys, sometimes permanently damaging them and causing kidney failure. These antibody pieces are called Bence Jones proteins. The increased number of cancerous cells can lead the body to produce too much uric acid. Excess uric acid is excreted in the urine, which can lead to kidney stones. Deposits of antibody pieces in the kidneys or other organs can lead to amyloidosis.
In rare instances, multiple myeloma interferes with blood flow to the skin, fingers, toes, nose, kidneys, and brain because the blood thickens (hyperviscosity syndrome).
Multiple myeloma may be discovered even before a person has symptoms, when an x-ray performed for another reason shows a loss of bone density. Bone loss may be widespread or limited to scattered punched-out areas of a few bones.
Multiple myeloma is sometimes suspected because of symptoms, such as back pain or bone pain of other sites, fatigue, fevers, and bruising. Blood tests performed to investigate such symptoms may reveal that a person has anemia, a decreased white blood cell count, a decreased platelet count, or kidney failure.
The two most useful blood tests are serum protein electrophoresis and immunoelectrophoresis. They detect and identify an overabundance of a single type of antibody found in most people who have multiple myeloma. Doctors also measure the different types of antibodies, especially IgG, IgA, and IgM.
A bone marrow biopsy is almost always performed to confirm the diagnosis. Other blood tests are useful in determining the overall outlook for the person. Higher levels of certain proteins in the person's blood when the disease is diagnosed usually indicate a poorer outlook and are likely to affect treatment decisions.
Treatment and Outlook
Multiple myeloma remains incurable despite recent advances in therapy. Treatment is aimed at preventing or relieving symptoms and complications, destroying abnormal plasma cells, and slowing progression of the disease.
The most consistently helpful drugs for multiple myeloma are corticosteroids, such as prednisone or dexamethasone. In addition, chemotherapy slows the progression of multiple myeloma by killing the abnormal plasma cells. Because chemotherapy kills normal cells as well as abnormal ones, the blood cells are monitored and the drug doses are adjusted if the number of normal white blood cells and platelets decreases too much.
Melphalan, and less often cyclophosphamide, are the chemotherapy drugs most often given with corticosteroids. Vincristine and doxorubicin are also effective and may have less severe side effects, particularly on the bone marrow, than melphalan and cyclophosphamide. For people who have a good response to chemotherapy, the drug interferon-alpha may prolong the response somewhat but has little impact on survival.
Thalidomide and new drugs called proteosome inhibitors are being used as alternatives to the chemotherapy drugs that are usually given. Because these treatments are also toxic to normal blood cells made in the bone marrow, stem cells are collected from the person's blood before the high-dose chemotherapy is administered. Stem cells are unspecialized cells that transform into immature blood cells, which eventually mature to become red blood cells, white blood cells, and platelets. The collected stem cells are then returned (transplanted) to the person after the high-dose treatment. Generally, this procedure is so taxing that it is usually reserved for people who are younger than 75.
Strong analgesics and radiation therapy directed at the affected bones can help relieve bone pain. Radiation therapy may also prevent the development of fractures. Monthly intravenous administration of pamidronate or the more potent zoledronic acid (both are bisphosphonates, drugs that decrease the rate of bone loss) can reduce the likelihood of fractures. Most people with multiple myeloma receive pamidronate or zoledronic acid as part of their treatment forever. Staying active is also important; prolonged bed rest tends to accelerate bone loss and makes the bones more vulnerable to fractures. Most people can enjoy a normal lifestyle that includes most activities. Drinking plenty of fluids dilutes the urine and helps prevent dehydration, which can make kidney failure more likely.
People who have symptoms of infection—fever, chills, cough that produces sputum, or reddened areas of the skin—should seek attention from a doctor promptly because they may need antibiotics. Erythropoietin or darbepoietin, drugs that stimulate red blood cell formation, may adequately treat anemia. Those who have severe anemia may need transfusions of red blood cells. High levels of calcium in the blood can be treated with intravenous fluids and often require intravenous bisphosphonates. People who have high levels of uric acid in the blood may benefit from allopurinol, a drug that blocks the body's production of uric acid.
Treatment slows disease progression in more than 60% of people. The average survival is more than 3 years after the disease is diagnosed, but survival time varies widely depending on the symptoms and complications at the time of diagnosis and the response to treatment. Importantly, advances in treatment and better pain relievers have greatly improved quality of life. Occasionally, people who survive for many years after successful treatment of multiple myeloma develop leukemia or irreversible loss of bone marrow function. These late complications may result from chemotherapy and often lead to severe anemia and an increased susceptibility to infections and bleeding.
Because multiple myeloma is ultimately fatal, people with multiple myeloma are likely to benefit from discussions of end-of-life care. They may also want to have an advance directive in place.