Multiple Myeloma.

Multiple myeloma (MM) is an incurable plasma cell neoplasm characterized by the accumulation of malignant plasma cells in the bone marrow. In the vast majority of cases, this neoplastic proliferation of plasma cells produces a monoclonal protein or immunoglobulin fragment that can be detected in the blood, urine, or both. Signs and symptoms of MM can be related to the location of these cells as well as the excessive production of irrelevant monoclonal immunoglobulin. As the malignant plasma cells expand in the marrow, normal surrounding bone can dissolve as a result of stimulation of osteoclasts by a variety of cytokines. Damage to the bone can lead to pain, pathologic fractures, and hypercalcemia. Furthermore, normal bone marrow can be suppressed, in particular, erythropoiesis. Impairment of the immune system leads to decreased humoral immunity with increased risk of infection, particularly encapsulated organisms. The paraprotein itself can lead to problems, including hyperviscosity, amyloid, and renal damage. This disease typically occurs in individuals in the sixth or seventh decades, but can also be seen in younger people. Systemic therapy is palliative. For decades, chemotherapy was based on single agents or combinations of alkylating agents and steroids. Despite great enthusiasm, dose intensification is not curative in the majority of cases, but can prolong overall survival (OS) and event-free survival (EFS). Newer drugs, based on antiangiogenesis approaches and targeting cytokine pathways, have generated a great deal of interest. [ABSTRACT FROM AUTHOR]