Multiple myeloma: 2014 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. If end-organ damage is not present, the presence of 60% or more clonal plasma cells in the marrow is also considered as myeloma. 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 who are not candidates for transplant, initial therapy is given for approximately 12 to 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 patients with intermediate or high risk myeloma. Management of refractory disease: Patients with indolent relapse can be treated first with 2-drug or 3-drug combinations. Patients with more aggressive relapse often require therapy with a combination of multiple active agents.