Management of Multiple Myeloma
Multiple myeloma (MM) is a neoplasm of plasma cells that is characterized by tumour cell tropism of the bone marrow and production of monoclonal immunoglobulins (Ig) detectable in serum and/or urine. It often manifests as one or more of lytic bone lesions, monoclonal protein in the blood or urine, disease in the bone marrow, renal failure, anemia, and hypercalcemia. Better understanding of the biology of myeloma has led to the development of agents, such as bortezomib, CC-5013, and thalidomide, that target the myeloma cell and the bone-marrow microenvironment. Ongoing trials promise to define the roles of new agents, mini-allogeneic transplantation, and maintenance therapy.
Key words: bone marrow, biology, transplant, chemotherapy, multiple myeloma.
Introduction
Multiple myeloma (MM) is a neoplastic disorder characterized by proliferation of a single clone of plasma cells derived from B cells.1 There have been major changes in the treatment regimens in the last decade or so and, although MM still remains an incurable disease, new treatment options promise more hope for the people with this disorder.2
Epidemiology
MM represents one percent of all malignancies in whites and two percent in African-Americans. Among hematological malignancies, it constitutes 10% of the tumours and ranks as the second most frequently occurring hematological cancer in the United States after non-Hodgkin’s lymphoma. An estimate of 15,980 new cases of multiple myeloma will occur in the United States in 2005, resulting in 11,300 deaths.3 In Canada, approximately four to five new cases per 100,000 persons are diagnosed each year, and an estimated 590 people will die from this cancer in 2005.
The disease is twice as common in men as it is in women. The incidence is higher in African-Americans and lower in Asians than in Caucasians. The incidence of myeloma and other plasma cell disorders increases with advancing age. The median age at diagnosis is 68 years.4
Risk Factors
Exposure to ionizing radiation is the strongest single factor linked to an increased risk of MM. This has been documented in atomic bomb survivors with a five times greater incidence than the control group and a latent period of approximately 20 years from exposure. Exposure to metals, especially nickel; agricultural chemicals; benzene, petroleum products, and other aromatic hydrocarbons; and silicon have been considered as potential risk factors. Alcohol and tobacco consumption has not been clearly linked to myeloma. Among medications, only mineral oil used as a laxative has been reported to be associated with an increased risk of MM in some patients.
Clinical Manifestations
Patients with MM may be entirely asymptomatic and diagnosed on routine blood testing or may present with myriad symptoms including fatigue due to anemia, frequent infections due to low uninvolved immunoglobulin or low CD4 count, and bone pain due to pathologic fracture.1 Renal failure can manifest as nausea and vomiting. Patients can present with paraplegia or nerve compression secondary to cord compression or neurological involvement (Table 1).
Biology of Multiple Myeloma
The bone-marrow microenvironment consists of extracellular matrix proteins, osteoblasts, osteoclasts, stromal cells, myeloma cells, vascular endothelial cells, and lymphophytes. The complex interactions between the myeloma cells, stromal cells, and adhesion molecules lead to production of cytokines and the factors involved in angiogenesis, thereby playing a key role in the pathogenesis of MM. Interleukin-6 (IL-6) is an important cytokine in myeloma cell growth and proliferation.5 Interaction between myeloma