To describe the clinical spectrum, neural autoantibody profile, and outcomes in patients with neurological immune-related adverse events (nirAE) from immune checkpoint inhibitor (ICI) therapy for cancer.

ICI enhance endogenous immune responses against cancer and sometimes lead to autoimmunity.

We retrospectively identified patients with nirAE among: 1) those seen at the Mayo Clinic Neurology Department (clinical cohort); and 2) those whose serum/cerebrospinal fluid was referred to the Mayo Clinic Neuroimmunology Laboratory for neural autoantibody screening (laboratory cohort).

Sixty-three patients were identified: clinical cohort, 39; laboratory cohort, 24. Median age at nirAE onset was 65 years (range, 31-86); 40% were female. Clinical presentations included central nervous system (CNS)-restricted manifestations (n=26), neuromuscular (n=30) or combined (n=5); 2 had isolated retinopathy. Specificities of detected neural autoantibodies,  in 24/31 patients with CNS involvement (clinical cohort, 7/13 [54%]; laboratory cohort 17/18 [94%]), included  amphiphysin, collapsin response-mediator protein-5, glutamic acid-decarboxylase-65, glial fibrillary acidic protein, neuronal intermediate filaments, leucine-rich glioma-inactivated-1, N-methyl-D-aspartate receptor, phosphodiesterase-10A, SOX1, and as yet unidentified neural-tissue-restricted autoantibodies. At a median of 10 months from onset (range, 0.5-46), 14 in the clinical cohort (36%) had an unfavorable outcome (severity-grade≥3); their characteristics were: onset-age ≥70 years, no immunosuppressive treatment, CNS involvement, lung cancer, higher initial severity-grade, shorter follow-up, and lack of systemic immune complications. By multivariate analysis, only older age remained independently associated with poor outcome (p=0.007).  Five patients had pre-existing paraneoplastic neurological autoimmunity (cerebellar ataxia; limbic encephalitis; encephalomyelitis and peripheral neuropathy; myasthenia gravis and retinopathy); all but the retinopathy patient experienced irreversible worsening despite immunosuppression and ICI cessation.

The spectrum of nirAE is broad; neural autoantibodies are common with CNS involvement (>50% in a clinical context). One-third of patients have a poor neurological outcome, mainly predictable by their pre-ICI-treatment characteristics and nirAE phenotype.