Reversible cerebral vasoconstriction syndrome following ciltacabtagene autoleucel therapy for relapsed multiple...

Ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T therapy, is approved for relapsed/refractory multiple myeloma (RRMM). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are common, but reversible cerebral vasoconstriction syndrome (RCVS) is a previously unreported complication following cilta-cel. A 63-year-old female with RRMM (IgA lambda, t(14;16)), no vascular risk factors, received cilta-cel after two prior therapies, including autologous transplantation. On day +10 post-CAR-T infusion, she developed grade 1 CRS, managed with tocilizumab and vasopressors, including midodrine. On day +19, she presented with headache, leg weakness, and loss of fine motor skills. Neuroimaging showed multifocal cerebral stenosis and ischemic strokes, initially suggesting vasculitis. Subsequent imaging confirmed RCVS (RCVS2 score 9). Treatment with corticosteroids, anakinra, siltuximab, cyclophosphamide, verapamil, and nimodipine failed to halt neurological decline, resulting in right-sided hemiplegia and Gerstmann's and Balint's syndromes. By day +69, CT angiography showed resolved stenosis, but neurological deficits persisted. This case identifies RCVS as a novel, life-threatening complication following cilta-cel, possibly linked to CRS, tocilizumab, or midodrine. It underscores the need for broader differential diagnoses and tailored management for CAR-T neurotoxicities, warranting further research.