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.
Treatment often includes some combination of conventional chemotherapy drugs, corticosteroids, and one or more of the following: proteasome inhibitors (such as bortezomib, carfilzomib, or ixazomib), immunomodulatory drugs (such as lenalidomide, thalidomide, or pomalidomide), a nuclear export inhibitor selinexor, or monoclonal antibodies (including daratumumab, isatuximab, or elotuzumab).
Plasma cells develop from B cells (B lymphocytes B cells One of the body's lines of defense ( immune system) involves white blood cells (leukocytes) that travel through the bloodstream and into tissues, searching for and attacking microorganisms and... read more ), a type of white blood cell that normally produces antibodies Antibodies One of the body's lines of defense ( immune system) involves white blood cells (leukocytes) that travel through the bloodstream and into tissues, searching for and attacking microorganisms and... read more (immunoglobulins). Antibodies are proteins that help the body fight infection. If a single plasma cell B cells One of the body's lines of defense ( immune system) involves white blood cells (leukocytes) that travel through the bloodstream and into tissues, searching for and attacking microorganisms and... read more multiplies excessively, the resulting group of genetically identical cells (called a clone) produces a large quantity of a single type of antibody Antibodies One of the body's lines of defense ( immune system) involves white blood cells (leukocytes) that travel through the bloodstream and into tissues, searching for and attacking microorganisms and... read more . 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 Overview of Plasma Cell Disorders Plasma cell disorders are uncommon. They begin when a single plasma cell multiplies excessively. The resulting group of genetically identical cells (called a clone) produces a large quantity... read more .)
The average age of people with multiple myeloma is about 65. 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 B cells One of the body's lines of defense ( immune system) involves white blood cells (leukocytes) that travel through the bloodstream and into tissues, searching for and attacking microorganisms and... read more 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 White Blood Cells The main components of blood include Plasma Red blood cells White blood cells Platelets read more , red blood cells Red Blood Cells The main components of blood include Plasma Red blood cells White blood cells Platelets read more , and platelets Platelets The main components of blood include Plasma Red blood cells White blood cells Platelets read more (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.
Fractures may occur if plasma cell tumors cause loss of bone density (osteopenia or osteoporosis Osteoporosis Osteoporosis is a condition in which a decrease in the density of bones weakens the bones, making breaks (fractures) likely. Aging, estrogen deficiency, low vitamin D or calcium intake, and... read more ) and weaken bones.
In addition, calcium released from the bones may result in abnormally high levels of calcium Hypercalcemia (High Level of Calcium in the Blood) In hypercalcemia, the level of calcium in blood is too high. A high calcium level may result from a problem with the parathyroid glands, as well as from diet, cancer, or disorders affecting... read more 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 Overview of Anemia Anemia is a condition in which the number of red blood cells is low. Red blood cells contain hemoglobin, a protein that enables them to carry oxygen from the lungs and deliver it to all parts... read more , 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 Overview of Kidney Failure This chapter includes a new section on COVID-19 and acute kidney injury (AKI). Kidney failure is the inability of the kidneys to adequately filter metabolic waste products from the blood. Kidney... read more . 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 Amyloidosis Amyloidosis is a rare disease in which abnormally folded proteins form amyloid fibrils that accumulate in various tissues and organs, sometimes leading to organ dysfunction, organ failure, and... read more , 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 Symptoms Macroglobulinemia is a plasma cell cancer in which a single clone of plasma cells produces excessive amounts of a certain type of large antibody (IgM) called macroglobulins. Although many people... read more ).
Diagnosis of Multiple Myeloma
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 Overview of Anemia Anemia is a condition in which the number of red blood cells is low. Red blood cells contain hemoglobin, a protein that enables them to carry oxygen from the lungs and deliver it to all parts... read more , a decreased white blood cell count Overview of White Blood Cell Disorders White blood cells (leukocytes) are an important part of the body’s defense against infectious organisms and foreign substances ( the immune system). To defend the body adequately, a sufficient... read more , a decreased platelet count Overview of Thrombocytopenia Thrombocytopenia is a low number of platelets (thrombocytes) in the blood, which increases the risk of bleeding. Thrombocytopenia occurs when the bone marrow makes too few platelets or when... read more , or kidney failure Overview of Kidney Failure This chapter includes a new section on COVID-19 and acute kidney injury (AKI). Kidney failure is the inability of the kidneys to adequately filter metabolic waste products from the blood. Kidney... read more .
The most useful laboratory tests are protein electrophoresis and immunoelectrophoresis 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 different types of antibodies, especially IgG, IgA, and IgM. IgD and IgE types of multiple myeloma are extremely 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 Bone Marrow Examination Red blood cells, most white blood cells, and platelets are produced in the bone marrow, the soft fatty tissue inside bone cavities. Sometimes a sample of bone marrow must be examined to determine... read more 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 as part of staging.
Even if x-ray findings suggest the diagnosis, 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.
Prognosis of Multiple Myeloma
Currently, no cure is available for multiple myeloma, but most people respond to treatment. The number of effective treatments has increased, and as a result, the average survival has nearly doubled. But survival time varies widely depending on certain features at the time of diagnosis and response to treatment, including
Blood levels of certain proteins, including beta2-microglobulin, serum albumin, and lactate dehydrogenase (LDH)
Genetic characteristics in the cancerous plasma cells, including specific chromosomal abnormalities and changes in genes
Newer drugs 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 Overview of Leukemia Leukemias are cancers of white blood cells or of cells that develop into white blood cells. White blood cells develop from stem cells in the bone marrow. Sometimes the development goes awry... read more 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 Introduction to Death and Dying Death is an intrinsic part of life, and talking about the likely outcomes of illness, including death and dying, is an important part of health care. Doctors and patients vary in the language... read more that involve their doctors and appropriate family and friends. Points for discussion may include advance directives Advance Directives Health care advance directives are legal documents that communicate a person’s wishes about health care decisions in the event the person becomes incapable of making health care decisions. There... read more , the use of feeding tubes, and pain relief.
Treatment of Multiple Myeloma
Some combination of different types of drugs (for example, corticosteroids with one of the immunomodulatory agents thalidomide, lenalidomide or pomalidomide, and/or proteasome inhibitors bortezomib, carfilzomib, or ixazomib, or the nuclear export inhibitor selinexor). In addition, traditional chemotherapy drugs may be also be used in combination with these types of drugs.
Monoclonal antibodies (for example, elotuzumab, isatuximab, and daratumumab) most commonly combined with steroids and an immunomodulatory agent or proteasome inhibitor
Possibly stem cell transplantation
Possibly radiation therapy to treat bone pain
Treatment of complications
Multiple myeloma remains incurable despite recent remarkable 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 patients 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 drugs are usually used to slow the progression of multiple myeloma by killing the abnormal plasma cells. Doctors use different combinations of drugs depending on characteristics of the myeloma and whether or not people are eligible for stem cell transplantation. Combinations may include drugs from more than one or each of the following:
An immunomodulatory agent (thalidomide, lenalidomide, or pomalidomide), and/or proteasome inhibitor (bortezomib, carfilzomib, or ixazomib), plus corticosteroids (such as dexamethasone, prednisone, or methylprednisolone)
More traditional chemotherapy drugs
The monoclonal antibodies elotuzumab, isatuximab, and daratumumab
Traditional chemotherapy drugs include an alkylating agent (melphalan, cyclophosphamide, or bendamustine) or anthracycline (doxorubicin or its pegylated liposomal formulation). Because chemotherapy kills normal cells as well as abnormal ones, the person's blood cell counts are monitored and the dose is adjusted if the number of normal white blood cells and platelets decreases too much.
Sometimes doctors recommend stem cell transplantation Stem Cell Transplantation Stem cell transplantation is the removal of stem cells (undifferentiated cells) from a healthy person and their injection into someone who has a serious blood disorder. (See also Overview of... read more for people who have good underlying health and in whom the myeloma has responded to several cycles of drug treatment. 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. However, many of the newer drug combinations are highly effective, so stem cell transplantation is now being 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 impact the ability of the patient to be treated with antimyeloma drugs. Monthly intravenous administration of pamidronate (a bisphosphonate—a drug that slows loss of bone density) or the more potent drug zoledronic acid can reduce the development of bone complications, and most people with multiple myeloma receive these drugs as part of their treatment forever. Monthly denosumab may be an option for patients who do not tolerate zoledronic acid or have poor renal function. People are encouraged to take calcium and vitamin D supplements to help reduce bone loss as long as they do not have high levels of calcium in their blood, and doctors encourage them to stay active because these actions help prevent bone loss. 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 do develop kidney problems may benefit from plasma exchange Plasma exchange In apheresis, blood is removed from a person and then returned after substances are removed from it. Apheresis can be used to Obtain healthy blood components from a donor to transfuse to a person... read more .
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 virus Shingles Shingles is a painful skin rash caused by a viral infection that results from reactivation of the varicella-zoster virus, the virus that causes chickenpox. What causes the virus to reactive... read more , especially when they are treated with specific antimyeloma drugs such as any of the proteasome inhibitors (including bortezomib, carfilzomib, or ixazomib) or the monoclonal antibodies (including daratumumab or elotuzumab). An oral antiviral drug called acyclovir taken long-term may help prevent herpes infections. Because people are at increased risk of infection, they should receive pneumococcal and influenza vaccines.
People who have severe anemia Overview of Anemia Anemia is a condition in which the number of red blood cells is low. Red blood cells contain hemoglobin, a protein that enables them to carry oxygen from the lungs and deliver it to all parts... read more may need transfusions of red blood cells. Erythropoietin or darbepoietin, drugs that stimulate red blood cell formation, may adequately treat the anemia in some people. Some people with anemia also may benefit from being given 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.
People who have high levels of uric acid in the blood or widespread disease may benefit from allopurinol, a drug that blocks the body's production of uric acid, which can damage the kidneys.