CAR T-cell therapy to treat multiple myeloma: current state and future directions.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy represents a transformative advancement in treating relapsed or refractory multiple myeloma (MM) in both early- and late-line settings. MM, a plasma cell malignancy, traditionally requires ongoing complex drug regimens, posing significant burdens on patients. In contrast, CAR T-cell therapy offers a one-time treatment option without the need for continuous maintenance therapy. CAR T-cell therapy leverages engineered T-cells to target specific antigens on tumor cells, leading to their elimination. Current approved therapies target B-cell maturation antigen (BCMA); new targets are under investigation, such as G-protein-coupled receptor class C group 5 member D (GPRC5D). Despite its efficacy, CAR T-cell therapy is associated with serious toxicities such as cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS), necessitating careful management. The review will provide an overview of the design and manufacturing of CAR T-cells and current FDA indications, as well as challenges and future directions of CAR-T therapy for MM treatment.