Cancer - Oncology

What is Multiple Myeloma?

Multiple myeloma is a cancer of plasma cells. Plasma cells are blood cells that form in the bone marrow, the soft, sponge-like tissue in the center of most bones. Bone marrow produces three types of blood cells: white blood cells, red blood cells, and platelets. Plasma cells develop from B lymphocytes (B cells), a type of white blood cell that is part of the body’s immune system.

Multiple myeloma begins when a plasma cell becomes abnormal and divides in an uncontrolled fashion. The abnormal plasma cells are known as myeloma cells. As they multiply, they crowd out normal, healthy cells. Plasma cells typically comprise less than five percent of the cells in the bone marrow. In multiple myeloma the percentage of plasma cells increases to more than 10 percent.

The increased number of abnormal plasma cells can lead to bone destruction and high levels of calcium in the blood (hypercalcemia). The abundance of abnormal plasma cells can also interfere with the functioning of other blood cells:

  • Red blood cells that carry oxygen to tissues throughout the body
  • White blood cells that fight infection and disease
  • Platelets that form blood clots to stop bleeding

Normal plasma cells, as part of the immune system, produce antibodies that fight infections and diseases. Malignant plasma cells, or myeloma cells, produce an abnormal antibody known as M protein (also called monoclonal protein) that collects in blood and urine. The M protein does not help fight infection. It can cause the blood to thicken and it can damage the kidneys.

The level of M protein in the blood and urine is measured as an indicator of myeloma activity and response to treatment. It is referred to as an M-spike. In some patients myeloma cells do not produce M protein, in which case the level of disease activity must be assessed differently.

Since myeloma cells typically are found throughout the body, the disease is referred to as multiple myeloma. However, the terms “myeloma” and “multiple myeloma” are often used interchangeably.

Conditions of Multiple Myeloma

Monoclonal Gammopathy of Undetermined Significance (MGUS)

In MGUS, less than 10 percent of the bone marrow is made up of abnormal plasma cells. As in myeloma, the abnormal plasma cells make M protein, which is sometimes detected during a routine blood or urine test. In most patients, the amount of M protein stays the same, there are no symptoms or health problems, and treatment is not required. The risk of MGUS increases with age. Approximately 3 percent of adults 50 and older and 5 percent of adults 70 and older have M-protein in their blood. While MGUS is considered a benign condition, myeloma typically develops in 1 to 2 percent of MGUS patients each year. It is important to monitor MGUS on a regular basis and to be on the alert for symptoms such as bone pain and fatigue that may develop.

Smoldering Multiple Myeloma (SMM)

SMM, an asymptomatic precursor to multiple myeloma, is characterized by increased levels of plasma cells in the bone marrow—10 percent or more— and higher than normal levels in the blood of M protein, the abnormal protein produced by plasma cells. Patients do not typically have symptoms, although mild tingling in the hands and feet might be experienced by some. SMM is usually detected through routine blood work. Like myeloma and MGUS, SMM is more common in men than women and is more common in African Americans. It accounts for about 15 percent of all cases of newly diagnosed myeloma. As is the case with MGUS, it is important to monitor SMM on a regular basis and to be on the alert for symptoms such as bone pain and fatigue. SMM is divided into two categories, low-risk and high-risk, as determined by molecular genetics and other diagnostic testing conducted on tissue samples from a patient’s bone marrow.

High-risk SMM tends to progress to myeloma more quickly than low-risk SMM, and therefore needs to be monitored more frequently. A subset of high-risk SMM patients, reclassified in 2014 by the International Myeloma Working Group as myeloma based on molecular biomarkers, may experience significantly increased risk of progression within two years. We are investigating whether this subset of patients may benefit from early treatment before symptoms occur.

Plasma Cell Neoplasms

Multiple myeloma, MGUS, and smoldering myeloma are plasma cell neoplasms. A neoplasm is an abnormal mass of tissue that results when cells divide more than they should or do not die when they should. A plasma cell neoplasm is a disease in which the body makes too many plasma cells. MGUS and smoldering myeloma are plasma cell neoplasms that are considered benign precursors to myeloma. Other malignant plasma cell neoplasms include plasmacytoma, Waldenstrom Macroglobulinemia, and amyloidosis. At Mount Sinai we treat all of these conditions, as well as related diseases such as Castleman Disease and POEMS Syndrome.

  • A plasmacytoma forms when the abnormal plasma cells are in one place and form one tumor. There are two types of plasmacytoma. In an isolated plasmacytoma of bone, one plasma cell tumor is found in the bone. Less than 10 percent of the bone marrow is made up of plasma cells and there are no other signs of cancer. Over time, plasmacytoma of the bone often becomes multiple myeloma. Plasmacytoma of bone can cause pain or broken bones. In extramedullary plasmacytoma, one plasma cell tumor is found in soft tissue but not in the bone or the bone marrow. Extramedullary plasmacytomas commonly form in tissues of the throat, tonsil and paranasal sinuses. They can cause pain or other problems, such as difficulty swallowing.
  • Waldenstrom Macroglobulinemia (Waldenstrom’s) is an indolent (slow-growing) type of non-Hodgkin lymphoma characterized by abnormal levels of monoclonal immunoglobulin (IgM) proteins in the blood and an enlarged liver, spleen, or lymph nodes. A cancer of B lymphocytes (B cells)—a type of white blood cell that is part of the immune system— Waldenstrom’s is also called lymphoplasmacytic lymphoma. In Waldenstrom’s, the malignant B cells build up in the liver, spleen and lymph nodes, causing them to swell. They also grow in the bone marrow, crowding out normal red cells, white cells, and platelets. The abnormal amount of IgM protein in the blood can cause it to become thick which can cause problems with blood flow in small blood vessels. Waldenstrom macroglobulinemia is rare, with an incidence rate of about 3 cases per million people per year in the United States. About 1,000 to 1,500 people are diagnosed with Waldenstrom’s each year in the United States. Since Waldenstrom’s grows slowly it can be well-controlled when diagnosed early.
  • Multiple myeloma and other plasma cell neoplasms may cause amyloidosis. Amyloidosis occurs when antibody proteins stick together in peripheral nerves and organs such as the kidney and heart. This can cause the nerves and organs to become stiff and unable to function properly.

Related Conditions

POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes) is a rare, multi-system condition associated with plasma cell neoplasms. It is characterized by overproduction of plasma cells, which can cause damage to the nerves, liver and spleen, diabetes or thyroid problems, and skin rashes.

Castleman Disease is a rare disease of lymph nodes and related tissues that results from the overgrowth of benign cells in the body’s lymphatic system (the tissues and organs that produce, store and carry white blood cells that fight infections and other diseases). In Unicentric Castleman Disease, only one group of lymph nodes in one part of the body — usually the chest or abdomen — is affected. In Multicentric Castleman Disease many groups of lymph nodes and lymphoid tissue throughout the body are affected and the immune system is weakened. Castleman Disease involving plasma cells tends to be multicentric. Patients with Multicentric Castleman Disease are at increased risk of developing lymphoma.


Multiple myeloma is a relatively uncommon cancer, although it is the second most common blood cancer. In the United States, the lifetime risk of getting multiple myeloma is 1 in 143 (0.7 percent). The American Cancer Society estimate for new cases in the United States in 2017 is 30,280—17,490 men and 12,790 women.

Multiple myeloma is most common in people over the age of 50. Males and African Americans are at increased risk. There are uncommon family clusters of multiple myeloma, suggesting that some risk factors may be inherited, but these factors have not been identified yet.

Conditions that can progress to myeloma include monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma. We monitor patients with these conditions on a regular basis so that intervention can be started if needed.