Toxicities of CAR-T, Bispecific Antibodies, and Antibody-Drug Conjugates in Multiple Myeloma: A Practical Approach to Risk Mitigation and Management.
Toxicities of CAR-T, Bispecific Antibodies, and Antibody-Drug Conjugates in Multiple Myeloma: A Practical Approach to Risk Mitigation and Management.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Windsor, CA · Author affiliation
Department of Biomedical Science, Faculty of Science, University of Windsor, Windsor, ON N9B 3P4, Canada.Location evidence
London, CA · Author affiliation
Department of Oncology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5W9, Canada.Location evidence
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Original abstract
B-cell maturation antigen (BCMA), G protein-coupled receptor class C group 5 member D (GPRC5D)-directed immunotherapies, chimeric antigen receptor T-cell (CAR-T) products, bispecific T-cell engagers (BsAbs), and antibody-drug conjugates (ADCs), have transformed the management of MM. Their adoption is now extending beyond tertiary centers following FDA modifications for CAR-T safety and the rapid uptake of off-the-shelf bispecifics suitable for community delivery. Clinicians outside specialist hubs must therefore be conversant with the full toxicity spectrum, including rare but high-consequence events, both for informed consent and for the work-up of post-therapy complications. In this narrative review, we report on the published literature around toxicities of approved and investigational BCMA- and GPRC5D-directed therapies, drawing on pivotal trial data, real-world cohorts, pharmacovigilance studies, and consensus management recommendations, with emphasis on practical recognition and risk mitigation. This review presents toxicities by a temporal pattern including acute (CRS, ICANS, infection, ocular, mucocutaneous), subacute (cranial nerve palsies, parkinsonism, myelitis, peripheral neuropathies IEC-associated enterocolitis and cardiovascular events), and long-term (prolonged cytopenias, second primary malignancies). We discuss validated risk stratification tools, such as the CAR-HEMATOTOX score, EASIX index, and multidisciplinary geriatric assessment, which predicts severe ICANS, infection, and resource utilization, supporting individualized pre-treatment planning. Safe delivery of immune therapies in community settings requires infrastructure for acute critical care, neurology, ophthalmology, infectious disease and long-term surveillance, but is achievable when paired with validated risk stratification and clear referral pathways.