Neurological implications of chimeric antigen receptor-T cell therapy

Chimeric antigen receptor (CAR)-T cell therapies have transformed the management of relapsed or refractory haematological malignancies and are now being adapted for severe B-cell mediated autoimmune disease, including neuroimmunological disorders. Their appeal lies in deep and durable B-cell depletion within lymphoid tissues and target organs, with the potential to induce long-lasting, treatment-free remission. At the same time, broader application is constrained by serious toxicities, in particular, neurological complications such as immune effector cell-associated neurotoxicity syndrome (ICANS) and more recently recognised movement, cerebellar, cranial nerve and peripheral nerve syndromes. In this review, we outline the biological principles of CAR-T cell therapy and summarise the emerging experience in neuroimmunology. We draw on data from both oncology and early autoimmune trials to describe the clinical spectrum, timing and proposed mechanisms of CAR-T cell-related neurotoxicity and to distinguish ICANS from later and more focal toxicities. As CAR-T cell therapies move from cancer centres into the care of patients with refractory neuroimmunological disease, neurologists will need a detailed understanding of both their therapeutic promise and their neurological risks, and close collaboration within multidisciplinary teams will be essential to deliver these treatments safely.