Shifts in the therapeutic paradigm for patients newly diagnosed with multiple myeloma: maintenance therapy and overall survival.

High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is the standard of care for eligible newly diagnosed multiple myeloma (MM) patients. Several randomized studies showed a survival advantage for patients undergoing transplantation, compared with conventional chemotherapy. Introduction of new drugs in this setting has markedly increased survival rates within the last 10 years. Efforts to further improve response rates and survival in those patients are still needed, mainly by increasing the depth of tumor reduction and the duration of response through more effective induction, consolidation, and maintenance therapies. Nevertheless, this approach is currently challenged by the promising results of long-term treatment with novel agents. Recent data suggest that the upfront combination of a proteasome inhibitor plus 1 immunomodulatory compound (IMiD) is highly effective. The combination of bortezomib, thalidomide, and dexamethasone (VTD) has proven to be highly effective as a frontline treatment and is significantly superior to vincristine, doxorubicin, and dexamethasone (VAD) or thalidomide and dexamethasone (Thal-Dex) before and after ASCT with a very manageable toxicity pattern. The most promising 3-drug association might be bortezomib, lenalidomide, and dexamethasone (VRD). Adjunction of a 4th drug has not proven to be more efficient. In patients not eligible for ASCT, the introduction of novel agents has changed the management of multiple myeloma. The combinations of melphalan, prednisone, and thalidomide and of bortezomib, melphalan, and prednisone have shown improved progression-free survival and overall survival in comparison with melphalan and prednisone alone. Melphalan, prednisone, and thalidomide and bortezomib, melphalan, and prednisone are now the new standards of care for elderly patients. Preliminary results also support the role of the combination of melphalan, prednisone, and lenalidomide followed by maintenance therapy with lenalidomide in the treatment of elderly patients. Physicians now have a wider variety of treatment options to tailor the most appropriate and efficacious treatment according to their patients' characteristics.