Treatment Options for Triple-class Refractory Multiple Myeloma

Abstract

The advent of new, more effective, and less toxic therapies has revolutionized the management of multiple myeloma in the past decade. Despite the availability of new treatments, most patients with multiple myeloma will become refractory to the therapies that currently comprise the hematologic standard of care for the malignancy, including proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies. Moreover, in recent years, a new subset of patients with multiple myeloma refractory to all 3 of these agents has emerged. This population, for whom a clear treatment paradigm has remained undefined, has been characterized by poor survival outcomes. The current approaches to the treatment of triple-class refractory disease are limited and include conventional chemotherapy, salvage autologous stem cell transplantation, and recycling previous regimens, each of which have generally had short-lived efficacy. It is anticipated that additional agents will be available for triple-refractory disease in the near future, including selinexor, chimeric antigen receptor T-cell therapy, and next-generation monoclonal antibodies. The development and further refinement of novel treatments for this subset of patients should be considered a key clinical and research priority.

Keywords: Autologous stem cell transplantation; Monoclonal antibodies; Relapsed myeloma; Selinexor; Triple-class refractory.