Future prospects of chimeric antigen receptor T-cell therapy for multiple myeloma

Although multiple myeloma (MM) remains an incurable hematological malignancy, the introduction of autologous stem cell transplantation, proteasome inhibitors, and immunomodulatory agents has increased the survival of patients. However, most patients will become refractory to available therapeutic regimens. Moreover, conventional strategies have shown limited benefit in high-risk patients with adverse cytogenetics. Therefore, novel strategies including immunotherapy are needed to improve the outcomes of these patients. Immunotherapy includes a range of strategies to redirect the immune system to attack tumor cells. Here, we review the most promising immunotherapy strategy published to date for many hematologic malignancies, chimeric antigen receptor (CAR) T cells. Most clinical studies of CAR T cell therapy for MM target B-cell maturation antigen (BCMA) on malignant plasma cells. The initial studies using BCMA targeted CAR T cells are devoted to patients with advanced relapsed/refractory MM. Eventual relapse after CAR T-cell therapy remains an issue. We present the most recent clinical data, as well as relevant preclinical data demonstrating novel strategies with the potential to improve clinical outcomes of cellular therapy for MM. Further, we present a proposal for how CAR T-cell therapy may fit into the future therapeutic landscape of MM as adoptive cellular therapy moves beyond the currently studied multiply relapsed/refractory setting.