Background and Aims

Neurological immune-related adverse events (N-irAEs) with varying frequency and severity have been reported in patients with cancer treated with immune-checkpoint-inhibitors (ICIs). Severe N-irAEs can be similar to paraneoplastic neurological syndromes, but their association with antineuronal antibodies is not well known.

To describe the neurological AEs after ICIs treatment, the frequency of antineuronal and glial antibodies and its clinical implication.

Methods

Case series studied in the laboratory of Hospital Clínic-IDIBAPS between Jan ‘18 and Oct ‘19. Onconeural, neuronal surface and glial antibody detection by rat brain immunohistochemistry, and confirmatory cell/immunoblot assays. Review of clinical features, type of cancer, ICI treatment and outcome.

Results

18 patients were referred from 10 different hospitals for antibody studies. 12 (67%) were men; median age 61.5 years (range 41-82). 12 (67%) had lung cancer, 3 melanoma, 1 prostate, 1 breast and 1 Hodgkin lymphoma. 6 (33%) patients received nivolumab, 5 (28%) pembrolizumab, 4 (22%) nivolumab + ipilimumab, 2 durvalumab and 1 atezolizumab. The clinical presentation was encephalitis/encephalopathy in 12 (67%), visual disturbances 2, encephalomyelitis 1, cerebellar ataxia 1, meningitis 1 and intestinal pseudo-obstruction 1. Anti-neural antibodies were detected in 5 (28%) patients: 1 anti-GABA_BR, 1 anti-Hu, 1 anti-Ma2 and 2 anti-GFAP. In 2 patients the antibodies were present before ICI initiation. The majority of cases received treatment with corticosteroids, with improvement of neurological symptoms.

Conclusions

Nearly 30% of patients with N-AEs have anti-neural antibodies, and their presence associates with characteristic clinical syndromes and suggests a paraneoplastic origin.