Neurological adverse events of immune checkpoint inhibitors and the development of paraneoplastic neurological syndromes.

Immune checkpoint inhibitors, a class of oncological treatments that enhance antitumour immunity, can trigger neurological adverse events closely resembling paraneoplastic neurological syndromes. Unlike other neurological adverse events caused by these drugs, post-immune checkpoint inhibitor paraneoplastic neurological syndromes predominantly affect the CNS and are associated with neural antibodies and cancer types commonly found also in spontaneous paraneoplastic neurological syndromes. Furthermore, post-immune checkpoint inhibitor paraneoplastic neurological syndromes have poorer neurological outcomes than other neurological adverse events of immune checkpoint inhibitors. Early diagnosis and initiation of immunosuppressive therapy are likely to be crucial in preventing the accumulation of neurological disability. Importantly, the neural antibodies found in patients with post-immune checkpoint inhibitor paraneoplastic neurological syndromes are sometimes detected before treatment, indicating that these antibodies might help to predict the development of neurological adverse events. Experimental and clinical evidence suggests that post-immune checkpoint inhibitor paraneoplastic neurological syndromes probably share immunological features with spontaneous paraneoplastic syndromes. Hence, the study of post-immune checkpoint inhibitor paraneoplastic neurological syndromes can help in deciphering the immunopathogenesis of paraneoplastic neurological syndromes and in identifying novel therapeutic targets.

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Declaration of interests AF, MVG, BJ, and JH are supported by the Fondation pour la recherche médicale (DQ20170336751) BETPSY project as part of the second Investissements d’Avenir programme (18-RHUS-0012), supported by a public grant overseen by the Agence Nationale de la Recherche. AF received a grant to perform research abroad by the European Academy of Neurology. ACG received grants or contracts from Project Data Sphere (neurologic immune related adverse events research funding), Biosensics (wearable sensor and digital technologies for quantitative assessment and remote monitoring of symptoms in myasthenia gravis grant), and National Institutes of Health (1R44NS122672–01A1, 5U54NS115054–03 MGFA) high impact pilot grant. AG received honoria and support to travel for itox retreat MD Anderson in 2022, Houston Methodist MGFA conference, and Grand Rounds (Umass, Cornell, Duke). AG participated on Data Safety Advisory Boards with Alexion, Argenx, and UCB pharma and Data Safety and Monitoring Board for Remote Monitoring and Management of Chemotherapy Induced Peripheral Neuropathy (REMOTE CIPN; NCT04763356). AG is chair of the Medical and Scientific Advisory Board (MGFA of New England). AV received a grant to perform research abroad by the European Academy of Neurology. AZ received grant for research by Roche and Genentech. AZ has a patent submitted on anti-DACH1 and anti-PDE10A as biomarkers of paraneoplastic autoimmunity. AZ received consulting fees (no personal remuneration) from Alexion Pharmaceuticals. JH receives royalties from licensing fees to Athena Diagnostics, Euroimmun, and ravo Diagnostika for a patent for the use of anti-CV2/CRMP5 as diagnostic tests. MVG is supported by the Fundación Martín Escudero to perform research abroad. All other authors declare no competing interests.