Current treatment of refractory and relapsed multiple myeloma.

In the past decade, previously approved novel agents, such as proteasome inhibitors (bortezomib) and immunomodulatory drugs ([IMiDs]; e.g., lenalidomide), have led to significant improvement in the treatment of multiple myeloma in Japan. However, almost all patients will ultimately relapse, even when they have achieved a deep and prolonged therapeutic response with initial treatment. Next-generation IMiDs (pomalidomide) and deacetylase inhibitors (panobinostat) were approved for use as salvage therapy for refractory and relapsed multiple myeloma [RRMM] within the last year. Long-term chemotherapy could result in the emergence of drug-resistant clones due to "intraclonal heterogeneity" and "clonal evolution by Darwinian selection." Though some recommendations on the management of RRMM have been detailed, no uniform treatment has yet been established for these patients. Relapse situations are heterogeneous. Therefore, relapse management requires an individual approach based on assessments of patient-, disease-, and treatment-related factors. The primary considerations when selecting an appropriate treatment are patient-related factors such as frailty, comorbidity, disability, quality of life, and the overall goals of care. We hope that these novel agents that appear promising in Japan, such as monoclonal antibodies (e.g., elotuzumab, daratumumab) and next-generation proteasome inhibitors (e.g., carfilzomib, ixazomib) will improve the outcomes of patients with this incurable disease in the near future.