Practical Approaches to the Management of Dual Refractory Multiple Myeloma

The outcome of myeloma patients' dual refractory to lenalidomide and bortezomib is generally poor and represents a significant clinical challenge with a clear need for new therapeutic approaches. This has prompted the development of next-generation proteasome inhibitors and immunodulatory drugs (IMiDs), as well as new classes of drugs with novel mechanisms of action. As a result, several of these agents have received regulatory approval that have shown promising activity in the dual refractory setting including the second-generation proteasome inhibitor carfilzomib and third-generation IMiD pomalidomide. Moreover, the regulatory approval of several first-in-class drugs for myeloma such as the histone deacetylase (HDAC) inhibitor panobinostat and the anti-CD38 monoclonal antibody daratumumab has further broadened the therapeutic landscape for these patients. Collectively, these advances have provided new treatment strategies in dual refractory myeloma as well as important insights for the development of future studies with rationally designed drug combinations to target this challenging patient population.