Multiple myeloma: 2013 update on diagnosis, risk-stratification, and management.

DISEASE OVERVIEW: Multiple myeloma accounts for approximately 10% of hematologic malignancies. DIAGNOSIS: The diagnosis requires 10% or more clonal plasma cells on bone marrow examination or a biopsy proven plasmacytoma plus evidence of associated end-organ damage. In addition, the presence of 60% or more clonal plasma cells in the marrow is also considered as myeloma regardless of the presence or absence of end-organ damage. RISK STRATIFICATION: In the absence of concurrent trisomies, patients with 17p deletion, t(14;16), and t(14;20) are considered to have high-risk myeloma. Patients with t(4;14) translocation are considered intermediate-risk. All others are considered as standard-risk. RISK-ADAPTED INITIAL THERAPY: Standard-risk patients can be treated with lenalidomide plus low-dose dexamethasone (Rd), or a bortezomib-containing triplet such as bortezomib, cyclophosphamide, dexamethasone (VCD). Intermediate-risk and high-risk patients require a bortezomib-based triplet regimen. In eligible patients, initial therapy is given for approximately 4 months followed by autologous stem cell transplantation (ASCT). Standard-risk patients can opt for delayed ASCT if stem cells can be cryopreserved. In patients are not candidates for transplant, initial therapy is given for approximately 12-18 months. MAINTENANCE THERAPY: After initial therapy, lenalidomide maintenance is considered for standard-risk patients who are not in very good partial response or better, while maintenance with a bortezomib-based regimen should be considered in pateints with intermediate or high-risk myeloma. 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.