Clinical development of CAR-T therapy for refractory multiple myeloma

Abstract

A chimeric antigen receptor (CAR) comprises an extracellular ligand recognition domain linked to CD3ζ and induces T-cell activation upon antigen binding. Recently, the potential of CD19-targeted CAR T-cells (CAR-T) to treat multiple myeloma has been explored. A group in the University of Pennsylvania reported that 4 out of 10 patients with refractory myeloma achieved an objective response (sCR: 1, VGPR: 1, and PR: 2). Although the resultant cancer ablation was an arresting sight, it remains unclear whether CD19 is a suitable target for myeloma. Therefore, CAR-T therapy employing alternative target antigens is being attempted. Some current clinical trials are utilizing CAR against differentiation antigens, including CD138, CD38, and kappa light chain. B-cell maturation antigen (BCMA) is also a potential candidate. A group in the NCI described 12 patients with refractory myeloma enrolled in a BCMA-CAR phase 1 clinical trial. Two patients receiving the highest dosage attained an objective response. Nevertheless, considerable research is required for CAR immunotherapy to become universally available to patients with myeloma. The current enthusiasm for the development of this cutting-edge technology is justified because extraordinary evidence indicates that it is effective, although this may not apply to every case. CAR-T therapy for myeloma is currently undergoing rapid, wide-scale growth both in academia and in industry-sponsored clinical development.