Triplet combinations in relapsed/refractory myeloma: update on recent phase 3 trials

Abstract

Multiple myeloma (MM) is a rare hematologic disease of antibody-secreting plasma cells. Our understanding of the pathogenesis of this malignancy has improved greatly, and at the same time, we have access to new and more effective treatments options. Over the last 5 years, a spectrum of novel therapies with different mechanisms of action, including third-generation immunomodulatory drugs (pomalidomide), second generation proteasome inhibitors (carfilzomib and ixazomib), a histone deacetylase inhibitor (panobinostat) and monoclonal antibodies (mAbs) (elotuzumab and daratumumab) has transformed our approach to the treatment of patients with relapsed/refractory MM (RRMM). Areas covered: In this review, we will summarize the characteristics of the new drugs used in RRMM with a specific focus on recent phase 3 trials of triplet combinations in this setting and the rationale behind the selection of one regimen over another. Expert commentary: Several recent phase III trials conducted with patients with RRMM have demonstrated that triplet combinations are associated with a deeper response and an increased duration of response compared to standard treatments. These effective regimens may control the emerging drug resistant clones leading to progression. However, they have distinct toxicity profiles, which need to be taken into account by patients and care givers. The landscape of RRMM is changing rapidly, and new standards of care are proposed.

Keywords: IMiDs; Multiple myeloma; monoclonal antibodies; phase 3; relapsed refractory.