Multiple myeloma is a cancer of plasma cells in which abnormal plasma cells multiply uncontrollably in the bone marrow and occasionally in other parts of the body.
People often have bone pain and fractures, and they may also have kidney problems, a weakened immune system (immunocompromise), weakness, and confusion.
Diagnosis is made by measuring the amounts of different types of antibodies in blood and urine and confirmed by a bone marrow biopsy.
Plasma cells develop from B cells (B lymphocytes), a type of white blood cell that normally produces antibodies (immunoglobulins). Antibodies are proteins that help the body fight infection. If a single plasma cell multiplies excessively, the resulting group of genetically identical cells (called a clone) produces a large quantity of a single type of antibody. Because this antibody is made by a single clone, it is called a monoclonal antibody and also is known as the M-protein. (See also Overview of Plasma Cell Disorders.)
The average age of people with multiple myeloma is about 70 years. Although its cause is not certain, the increased occurrence of multiple myeloma among close relatives indicates that heredity plays a role. Exposure to radiation is thought to be a possible cause, as is exposure to benzene and other solvents.
Normally, plasma cells make up less than 1% of the cells in the bone marrow. In multiple myeloma, typically the majority of bone marrow elements are cancerous plasma cells. The overabundance of these cancerous plasma cells in the bone marrow leads to the increased production of proteins that suppress the development of other normal bone marrow elements, including white blood cells, red blood cells, and platelets (cell-like particles that help the body form blood clots). In addition to producing a large amount of monoclonal antibody, the production of normal, defensive antibodies is markedly reduced.
Often, collections of cancerous plasma cells develop into tumors within bones. The cancerous cells also secrete substances that cause loss of bone, most commonly in the pelvic bones, spine, ribs, and skull. Infrequently, these tumors develop in areas other than bone, particularly in the lungs, liver, and kidneys.
Symptoms of Multiple Myeloma
Because plasma cell tumors often invade bone, bone pain, often in the back, ribs, and hips, may occur. Other symptoms result from the complications.
Complications
Fractures may occur if plasma cell tumors cause loss of bone density (osteopenia or osteoporosis) and weaken bones.
In addition, calcium released from the bones may result in abnormally high levels of calcium in the blood, possibly causing constipation, increased frequency of urination, kidney problems, weakness, and confusion.
The reduced production of red blood cells often leads to anemia, which causes fatigue, weakness, and paleness (pallor) and may lead to heart problems. Decreased production of white blood cells leads to repeated infections, which may cause fever and chills. Decreased platelet production 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 collecting system of the kidneys, sometimes permanently damaging them by interfering with their filtering function and leading to kidney failure. The light chain pieces of the antibody in the urine (or blood) are called Bence Jones proteins. The increased number of growing cancerous cells can lead to the overproduction and excretion of uric acid in the urine, which can lead to kidney stones. Deposits of certain types of antibody pieces in the kidneys or other organs can lead to amyloidosis, another serious disorder found in a small number of people with multiple myeloma.
In rare instances, multiple myeloma interferes with blood flow to the skin, fingers, toes, nose, kidneys, and brain because the blood thickens (hyperviscosity syndrome).
Diagnosis of Multiple Myeloma
Laboratory tests
Bone marrow biopsy
X-rays or other imaging studies (magnetic resonance imaging, and positron emission tomography combined with computed tomography)
Multiple myeloma may be discovered even before people have symptoms, when laboratory tests done for another reason show elevated protein levels in the blood or protein in the urine, or an x-ray done for another reason shows specific areas of bone loss. Bone loss may be widespread or, more often, appears as isolated punched-out areas in bones.
Multiple myeloma is sometimes suspected because of symptoms, such as back pain or bone pain in other sites, fatigue, fevers, and bruising. Blood tests done 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 most useful laboratory tests are protein electrophoresis and immunofixation of serum and urine. They detect and identify an overabundance of a single type of antibody found in most people who have multiple myeloma. Doctors also measure the levels of different types of antibodies, especially IgG and IgA. IgM, IgD, and particularly IgE types of multiple myeloma are rare. Calcium levels are usually measured as well.
A urine specimen collected over a 24-hour period is analyzed for the amount and types of protein in it. Bence Jones proteins, which represent part of the monoclonal antibody, are found in the urine of half of the people who have multiple myeloma.
A bone marrow aspirate and biopsy is done to confirm the diagnosis. In people with multiple myeloma, bone marrow specimens show a large number of plasma cells abnormally arranged in sheets and clusters. Individual cells also may appear abnormal.
In addition, other blood tests are useful in determining how advanced multiple myeloma is (staging). Certain changes in levels of specific protein (eg, higher levels of beta-2 microglobulin and lower levels of albumin) in the person's blood when the disease is diagnosed usually indicate the likelihood of a shortened survival and are likely to affect treatment decisions. In addition, specific chromosomal abnormalities and higher serum lactate dehydrogenase levels predict shortened survival.
Even if x-ray findings suggest the diagnosis, additional imaging is needed to determine what bones are affected. X-rays of the entire body (skeletal survey) are usually done. Magnetic resonance imaging (MRI) or positron emission tomography (PET) combined with computed tomography (CT) may also be done to examine specific sites of bone pain.
Treatment of Multiple Myeloma
Possibly stem cell transplantation (also called hematopoietic cell transplantation)
Possibly radiation therapy to treat bone pain
Treatment of complications
Multiple myeloma remains incurable despite major advances in therapy. Treatment is aimed at preventing or relieving symptoms and complications, destroying abnormal plasma cells, and slowing progression of the disorder.
Treatment usually does not begin until the person develops symptoms or complications, although certain people with high-risk features who are asymptomatic and have no obvious complications may also be required to start treatment. These high-risk features include greater extent of disease, blood levels of certain proteins, and specific genetic abnormalities in the tumor cells.
Several different medications are usually used to slow the progression of multiple myeloma by killing the abnormal plasma cells. Doctors use different combinations of medications depending on characteristics of the myeloma and whether or not people are eligible for stem cell transplantation. Combinations may include medications from more than one or each of the following:
More traditional chemotherapy agents
Sometimes doctors recommend stem cell transplantation for people who have good underlying health and in whom the myeloma has responded to several cycles of treatment with medications. Stem cells (unspecialized cells that transform into immature blood cells, which eventually mature to become red blood cells, white blood cells, and platelets) are collected from the person's blood before high-dose chemotherapy is given. These stem cells are then returned (transplanted) to the person after the high-dose treatment. Generally, this procedure is reserved for people who are younger than 70 years. However, many of the medication combinations are highly effective, so stem cell transplantation is used less often.
Strong analgesics and radiation therapy directed at the affected bones can help relieve bone pain, which can be severe. Radiation therapy may also prevent the development of fractures. However, radiation therapy may damage bone marrow function, which can make treatment with antimyeloma medications too risky to pursue.
Drinking plenty of fluids dilutes the urine and helps prevent dehydration, which can make kidney failure more likely. People who do develop kidney problems may benefit from plasma exchange to remove abnormal proteins (light chains) responsible for kidney damage.
People who have signs of infection—fever, chills, cough productive of sputum, or reddened areas of the skin—should seek medical attention promptly because they may need antibiotics. People also may be at risk of infections with the herpes zoster viruspneumococcal vaccine, influenza vaccine, COVID-19 vaccine, and the shingles (herpes zoster) vaccine.
People who have severe anemia may need transfusions of red blood cells. Erythropoietin or darbepoietin, medications that stimulate red blood cell formation, may adequately treat the anemia in some people. Some people with anemia also may benefit from iron supplements.
High levels of calcium in the blood can be treated with intravenous fluids and often require intravenous bisphosphonates. Avoiding vitamin D and calcium-containing foods also is helpful to reduce elevated calcium levels.
Prognosis for Multiple Myeloma
No cure is available for multiple myeloma, but most people respond to treatment. The number of effective treatments has increased, and as a result, many people live more than 10 years after diagnosis. But survival time varies widely depending on certain features at the time of diagnosis, including
Kidney problems
Blood levels of certain proteins, including beta 2-microglobulin, serum albumin, and lactate dehydrogenase (LDH)
Genetic characteristics in the cancerous plasma cells, including specific chromosomal abnormalities and changes in genes
Newer medications have lengthened survival in people with multiple myeloma. In addition, bisphosphonates given by infusion monthly to reduce bone complications, substances that stimulate the production of blood cells (growth factors) to increase the number of red and white blood cells, and better pain relievers have also greatly improved the 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 that involve their doctors and appropriate family and friends. Points for discussion may include advance directives, the use of feeding tubes, and pain relief.
