Guest editorial: understanding the pathogenesis and the evolving treatment paradigm for multiple myeloma in the era of novel agents

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1 Shifts in the therapeutic paradigm The introduction of thalidomide, lenalidomide, and bortezomib has significantly improved the response rates and survival outcome in patients with myeloma (MM), and been integrated into MM treatment [1‐3]. These new agents target not only the intracellular mechanisms in MM cells but also the interaction between MM cells and the bone marrow microenvironment. Given the clinical benefit of these novel agents either alone or in combinatorial regimens, the treatment of MM is changing rapidly. A focus of clinical studies appears to be the evaluation and identification of novel combinations using these new agents to uniformly produce better outcomes in different clinical settings of patients with MM, and to further tailor treatment as appropriate to the clinical background as well as the biological characteristics of MM cells and their surrounding microenvironment in individual patients. High-dose therapy with autologous hematopoietic stem cell transplantation (ASCT) is the standard of care for newly diagnosed MM patients eligible for ASCT. Introduction of new drugs in the induction setting have markedly improved response rates, leading to increased survival rates after ASCT. For newly diagnosed elderly patients, or those not eligible for ASCT, the introduction of novel agents has also changed the management of this disease. The combination of melphalan, prednisone, and thalidomide, and that of bortezomib, melphalan, and prednisone are regarded as the new standards of care for elderly patients [4]. However, no standard treatments have been established for relapsed/refractory MM, although it has been suggested that the implementation of treatment regimens based on proteasome inhibitors and/or immunomodulatory drugs (IMiDs) improves response rates and survival in patients with relapsed/refractory MM [5, 6]. Overall, recent data suggest that the upfront combination of individual proteasome inhibitors and IMiDs is highly effective, and new approaches with these novel agents are currently being studied to further improve the response rates and duration of response, including the implementation of induction therapies with three or more drugs in combination, and consolidation and maintenance therapies featuring long-term administration of novel agents. 2 Risk-stratification by cytogenetic and molecular profiling