Multiple Myeloma

Multiple myeloma is a devastating malignancy of plasma cells that was first described in 1848. It has diverse presentations but is characterized by anemia (a deficiency in the oxygen-carrying component of the blood), bone destruction, elevated blood calcium levels, and renal failure. It currently has no definitive cure, but a number of medications benefit patients.

Plasma cells are an integral part of the human immune system and are responsible for secreting antibodies. In multiple myeloma, normal plasma cells are replaced by cancerous plasma cells which function in a disregulated manner. They secrete non-functional antibodies collectively known as the M protein. These antibodies provide no aid in immune function, greatly increasing susceptibility to infections, especially from encapsulated (enclosed by a protective coating or membrane) organisms including Streptococcus pneumoniae and Neisseria menigitidis.

The neoplastic cells begin replacing the bone marrow thereby preventing the formation of cells derived from the marrow. This results in impaired red cell production causing anemia. Decreased white blood cell production further leads to infections and reduced platelet formation causes bleeding.

Bone pain and destruction is due to the cancerous plasma cells secreting substances which stimulate osteoclasts (the cells responsible for breaking down the bone.) This is a devastating complication burdening patients with fractures of the spine leading to spinal chord compression, severe bone pain and broken long bones. Because calcium is a major component of bones, the increased osteoclastic activity causes increased calcium in the blood. This excess calcium and direct injury to the renal tubules overload the kidneys and subsequently cause them to fail. Myeloma often results in a soft tissue masses (plasmacytomas) and occasionally they overwhelm the kidney as well.

Multiple myeloma is preceded by a condition named Monoclonal Gammopathy of Undetermined Significance (MGUS), in which a M protein can be detected, but the end-organ dysfunction characteristic of multiple myeloma is absent. The mechanisms that precipitate the transformation from MGUS to multiple myeloma are unclear.

Multiple myeloma accounts for approximately 10 percent of hematological malignancies and the annual incidence age-adjusted to the year 2000 population is 4.3 per 100,000 individuals with 15,000 new cases [Page 1146]each year. African American are affected around twice as much as whites and it is slightly more common in women. The median age of onset is 66 and the mean survival is approximately three years.

Treatment focuses on cancer suppression and on managing symptoms. Medication like bisphosphonates, which inhibit osteoclast function and prevent bone pain and destruction, along with erythropoietin, which stimulates red blood cell production, should be administered as needed. With infections, antibiotics should be used. Chemotherapy usually begins with an induction therapy aimed at lowering the tumor burden.

Subsequently, Autologous Stem Cell Transplant, where an individuals own stem cells are harvested, stored and later returned to them intravenously, is used and has been shown to be efficacious. The medication thalidomide with or without steroids, and the chemotherapeutic agent melphan are often used. Novel agents which have shown to be effective include Bortezomib, a drug called a proteosome inhibitor, and Lenalidomide, a drug similar to thalidomide and an immunomodulatory drug.

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