Pharmacogenetic studies in multiple myeloma

Multiple myeloma (MM) is a malignant plasma cell disorder that accounts for approximately 10% of all hematologic cancers.1-2 MM is characterized by clonal proliferation of malignant plasma cells in the bone marrow, which secrete a homogeneous immunoglobulin product known as monoclonal (M) protein or paraprotein. Typical features of MM include osteolytic bone lesions, renal disease, anemia, hypercalcemia and immunodeficiency.3 The pathological development of MM is a multistep process and starts with the emergence of an asymptomatic premalignant stage of clonal plasma cell proliferation known as “monoclonal gammopathy of undetermined significance” (MGUS), occurring in about 3% of individuals above the age of 50. MGUS cells secrete monoclonal immunoglobulin (Ig) which may progress to smouldering MM and ultimately to symptomatic intramedullary and extramedullary multiple myeloma, or plasma cell leukemia; expressing the same Ig. Smouldering MM has a stable intramedullary tumor cell content of >10%, but no osteolytic lesions or other complications of malignant MM. Patients with MGUS have a risk to progress to myeloma or a related malignancy at a rate of 1% a year.4-5 The prevalence of both MGUS and MM increases markedly with age, and is slightly more common in men than in women. The incidence is about two-fold higher in African Americans than in Caucasians. The median length of survival after diagnosis is approximately 3-5 years.