Biological and Translational Considerations regarding the Recent Therapeutic Successes and Upcoming Challenges for...

Even though multiple myeloma (MM) is still considered incurable, the therapeutic management of this disease has undergone a major transformation over the last two decades, with several new classes of therapeutics and diverse options for their combined use in many different regimens that have contributed to major improvement in overall survival of patients. This review discusses key themes underlying the pharmacological and immune-based therapies that represent the cornerstones of this progress. A major part of the clinical progress achieved by these classes' therapeutics has depended on the targeting of molecular pathways with distinct or preferential roles for the biology of plasma cells-normal or malignant-and the ability of many of these agents to be incorporated into combination regimens that exhibit enhanced antimyeloma responses, without precipitating acceptable levels of toxicity. This review also discusses why these advances have not yet translated into curative outcomes and how these remaining barriers could be overcome.