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Treatment of multiple myeloma
S. Vincent Rajkumar
Abstract | The treatment of multiple myeloma has changed dramatically in the past decade. The increasein the number of active agents has generated numerous possible drug combinations that can be usedinthe first-line and relapsed settings. As a result, there is considerable confusion about the choice of regimens for initial therapy, role of transplantation in the era of new drugs, end points for therapy, and the role ofmaintenance therapy. A hotly debated area is whether treatment approaches should achieve cure or disease control, which impacts greatly on the treatment strategy employed. This article provides an update on the treatment of multiple myeloma, with a focus on recent advances, newly diagnosed disease, role of transplantation and maintenance therapy. A synthesized approach to the treatment of myeloma is presented, along with a discussion of key paradigms that need to be challenged.
Rajkumar, S.V. Nat. Rev. Clin. Oncol. 8, 479491 (2011); published online 26 April 2011; corrected online 6 July 2011; http://wwwa.nature.com/doifinder/10.1038/nrclinonc.2011.63
Web End =doi:10.1038/nrclinonc.2011.63
Introduction
Multiple myeloma is a malignant monoclonal plasma cell disorder characterized by osteolytic bone lesions, anemia, hypercalcemia, and renal failure.1,2 It has an age-adjusted incidence of approximately four per 100,000 and accounts for 10% of all hematologic malignancies.3 The median age at diagnosis is approximately 65years, and the disease is more common in black people compared with white people.4 Unlike most other malignancies, the diagnosis of multiple myeloma is not histopathologic, but requires specific clinical features; multiple myeloma represents a clinicopathologic entity. Diagnosis involves evidence of a clonal plasma cell disorder (that is, 10% or more plasma cells on bone marrow examination or biopsy-proven plasma cytoma) and evidence of end-organ damage (hyper calcemia, renal insufficiency, anemia, or bone lesions) that can be attributed to the plasma cell disorder.5
Although multiple myeloma is considered to be a single disease, it consists of at least six non-
overlapping cyto-genetic subtypes (Table1). It is likely that with improved understanding of disease pathogenesis, each cytogenetic category will be considered a distinct entity for purposes of diagnosis and therapy. The cytogenetic subtypes are evident early in the course of the disease, and might be a precursor event associated with the transformation of normal plasma cells to the clonal pre malignant stage...