Peripheral Nerve Infiltration by CAR T-cells in a Case of Mononeuritis Multiplex after Ciltacabtagene Autoleucel

Delayed neurological toxicity, distinct from acute immune effector cell-associated neurotoxicity (ICANS), is an emerging complication of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-targeting CAR T-cell therapy. Peripheral nerve (PN) involvement has been described as cranial nerve palsies or Guillain-Barré-like syndromes, yet the underlying mechanisms remain poorly defined. We describe a case of asymmetric, immune-mediated multifocal PN involvement, clinically resembling autoimmune, T-cell-mediated mononeuritis multiplex (MNM), occurring after cilta-cel therapy. Several months post-infusion, the patient developed progressive asymmetric sensorimotor neuropathy preceded by bilateral facial nerve palsies. Electrodiagnostic studies confirmed multifocal axonal involvement, and nerve biopsy revealed Wallerian degeneration with CD3+ and CAR+ T-cell infiltration in the absence of BCMA expression on neural tissue. These findings suggest that delayed neurotoxicity may arise from immune-mediated, BCMA-independent mechanisms involving off-target tissue inflammation. Although CAR T-cells were detected within the affected nerve tissue, their pathogenic significance remains unclear and may reflect antigen-independent infiltration, immune activation or secondary bystander recruitment in the setting of immune dysregulation. The patient demonstrated marked neurological recovery following corticosteroids and cyclophosphamide, an immunosuppressive regimen modeled on MNM treatment. This case underscores the importance of comprehensive neurodiagnostic evaluation and early immunosuppression in managing delayed, non-ICANS CAR T-cell neurotoxicity.