Balancing Efficacy and Safety in Multiple Myeloma Patients Receiving B cell Maturation Antigen-Directed CAR T-Cell Therapy
Abstract
B-cell maturation antigen (BCMA) directed CAR T-cell therapy has emerged as an innovative and effective treatment for patients with relapsed/refractory multiple myeloma, demonstrating high response rates and durable remissions. However, its use is associated with a broad spectrum of toxicities, ranging from well characterized common events to rarer, less well described complications. A comprehensive understanding of both common and rare toxicities is essential for timely recognition and management to prevent non-relapse mortality. Frequently observed toxicities include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell-associated hematotoxicity, and infections. In addition, less frequent adverse events have been reported, including non-ICANS neurotoxicity such as parkinsonian-like movement disorders, immune-mediated enterocolitis, hemophagocytic lymphohistiocytosis, and secondary malignancies. The timing and severity of these toxicities is variable and may be influenced by the extent of CAR T-cell expansion and persistence, as well as patient-specific factors. In this review, we summarize currently available evidence with respect to the safety profile of approved BCMA-targeted CAR T-cell therapies, emphasizing both common and rare toxicities, their possible underlying mechanisms, and management strategies.
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