Cellular therapy for multiple myeloma: what's now and what's next

Despite sig nifi cant improve ment in the treat ment of mul ti ple mye loma (MM), a cure remains elu sive, and patients fail-ing proteasome inhib i tors, immu no mod u la tory drugs, and anti - CD38 mono clo nal antibodies remain a chal lenge due to a lack of stan dard of care treat ment and a dis mal sur vival rate. The devel op ment of T -cell redirecting ther a pies, includ-ing bispecific T -cell engagers and chi me ric anti gen recep tor (CAR) T cells, have transformed the out come of tri ple - class exposed relapsed and refrac tory MM (RRMM). B -cell mat u ra tion anti gen (BCMA) has proven to be an impor tant tar get in MM, and BCMA -directed CAR T cells have shown unprec e dented effi cacy with a prolonged dura tion of response in a pop u la tion with advanced RRMM, lead ing to the approval of 2 dif fer ent BCMA CAR T -cell prod ucts. Still, and in con trast to prior expe ri ence in the field of CD19 - directed CARs, no pla teau has been seen in the sur vival curves, and relapses con tinue to occur. Therefore, fur ther improve ment is needed. Early use in the course of the dis ease as well as of next -generation CARs may further augment the efficacy of these therapies. In this review we address current state-of-the-art approved BCMA -directed CAR T -cell ther apy in RRMM, as well as poten tial future devel op ments focused on opti miz ing patient care and novel CAR designs.