Sequencing of nontransplant treatments in multiple myeloma patients with active disease

The approval of several different classes of drugs in recent years has resulted in a dramatic expansion of treatment options for multiple myeloma patients, improving both survival and quality of life. Lenalidomide and bortezomib are now core components of treatment both at time of diagnosis and at relapse. Next-generation immunomodulatory drugs, like pomalidomide, and newer proteasome inhibitors like carfilzomib and ixazomib are available for use at relapse. Drugs with novel mechanisms of action such as the histone deacetylase inhibitor panobinostat and the monoclonal antibodies targeting SLAMF7 (elotuzumab) and CD38 (daratumumab) are significant steps forward. Recent clinical trials describing novel combinations of these drugs have demonstrated unprecedented improvements in efficacy while maintaining tolerability. All of these options provide not only a challenge for choice of therapy, but also the opportunity to aim for increasing depth of response. This chapter will describe an approach on how to sequence and incorporate these therapies, focusing on patients where high-dose melphalan and autologous stem cell transplant are deferred or not applicable.