CAR-T Cell Therapy: Engineering Remission in Refractory Myeloma

Abstract

Chimeric antigen receptor (CAR) T cells have rapidly reshaped the treatment of relapsed and refractory multiple myeloma (MM), progressing from an experimental salvage option to a therapy with a demonstrated overall survival advantage and durable, potentially curative remissions in a subset of patients. This review surveys the current evidence supporting their use, the biology underlying their successes and failures, established and emerging toxicities, and novel approaches that will define the field in the coming years. Approved products directed against B cell maturation antigen (BCMA) induce rapid and deep responses even in heavily pretreated patients, and long-term follow-up now suggests a meaningful fraction of patients achieve prolonged remission after a single infusion without maintenance therapy. These benefits are accompanied by distinctive toxicities that shape the risk-benefit calculus as therapy moves to earlier lines and even to treatment naïve patients. We discuss the determinants of response and relapse, as well as the mechanisms of antigen-positive and antigen-negative escape that next-generation approaches aim to overcome. These include novel antigen targets, multi-antigen and armored constructs, rapid manufacturing, and in vivo CAR generation, all with the goal of extending durable remissions to every patient.