Toxicities of CAR-T, Bispecific Antibodies, and Antibody–Drug Conjugates in Multiple Myeloma: A Practical Approach to Risk Mitigation and Management

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.