Multiple myeloma: 2012 update on diagnosis, risk-stratification, and management

Disease overview: Multiple myeloma accounts for similar to 10% of all hematologic malignancies. Diagnosis: The diagnosis requires 10% or more clonal plasma cells on bone marrow examination or a biopsy proven plasmacytoma plus evidence of end-organ damage felt to be related to the underlying plasmacell disorder. Risk stratification: Patients with 17p deletion, t(14; 16), t(14; 20), or high-risk gene expression profiling signature have high-risk myeloma. Patients with t(4; 14) translocation, karyotypic deletion 13, or hypodiploidy are considered to have intermediate-risk disease. All others are considered to have standard-risk myeloma. Risk-adapted therapy: Standard-risk patients are treated with nonalkylator-based therapy such as lenalidomide plus low-dose dexamethasone (Rd) followed by autologous stem-cell transplantation (ASCT). An alternative strategy is to continue initial therapy after stem-cell collection, reserving ASCT for first relapse. Intermediate- risk and high-risk patients are treated with a bortezomib-based induction followed by ASCT and then bortezomib-based maintenance. Patients not eligible for ASCT can be treated with Rd for standard risk disease, or with a bortezomib-based regimen if intermediate-risk or high-risk features are present. To reduce toxicity, when using bortezomib, the once-weekly subcutaneous dose is preferred; similarly, when using dexamethasone, the low-dose approach (40 mg once a week) is preferred, unless there is a need for rapid disease control. Management of refractory disease: Patients with indolent relapse can be treated first with two-drug or three-drug combinations. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. The most promising new agents in development are pomalidomide and carfilizomib. Am. J. Hematol. 87: 79-88, 2012. (C) 2011 Wiley Periodicals, Inc.