Neurological complications induced by immune checkpoint inhibitors: a comprehensive descriptive case-series unravelling high risk of long-term sequelae

• Published in: Brain communications 2021-10, Vol.3 (4), p.fcab220-fcab220
• Main Authors: Plaçais, Léo, Michot, Jean-Marie, Champiat, Stéphane, Romano-Martin, Patricia, Baldini, Capucine, Joao, Maria Silva, Marabelle, Aurélien, Voisin, Anne-Laure, Not, Adeline, Labeyrie, Céline, Beaudonnet, Guillemette, Laparra, Ariane, Maria, Alexandre T J, Masseau, Agathe, Dehette, Stéphanie, Deleporte, Amélie, Echaniz-Laguna, Andoni, Denier, Christian, Adams, David, Lambotte, Olivier, Noel, Nicolas, Cauquil, Cécile
• Format: Article
• Language: English
• Subjects: Life Sciences; Neurons and Cognition; Original; Pharmaceutical sciences
• ISSN: 2632-1297; 2632-1297
• DOI: 10.1093/braincomms/fcab220

Abstract Neurological immune-related adverse events are complications of programmed-cell death 1 or programmed-cell death 1 ligand immunotherapies that can be life threatening and often lead to anticancer immunotherapy withdrawal. Scant clinical data are available that integrate the clinical presentation, therapeutic management and long-term outcome. All consecutive adult patients treated by programmed-cell death 1 or programmed-cell death 1 ligand immunotherapies, given alone or in combination with other treatment, who experienced a neurological immune-related adverse event with a severity grade ≥2 in Paris Saclay-University hospitals were investigated from June 2014 to February 2019. The frequency of neurological immune-related adverse events was calculated from the prospective Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie cohort. Forty patients presenting with 51 distinct neurological immune-related adverse events were included. The prevalence of grade ≥2 neurological immune-related adverse events was estimated to be 1.22% in the Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie cohort. Among 40 patients with neurological immune-related adverse events, 65% received programmed-cell death 1 or programmed-cell death 1 ligand monotherapy and 35% received a combination of programmed-cell death 1 plus anti-CTLA4 (Common Terminology Criteria for Adverse Events). Clinical neurological presentations were peripheral (48%), central (35%), or mixed (18%). The severity of neurological immune-related adverse events was grade 2 for 14 (35%) and ≥grade 3 for 26 patients (65%). The mortality rate related to neurological immune-related adverse events was 8%. Corticosteroid treatment led to neurological recovery in 74%. Long-term follow-up highlighted that 53% of patients experienced long-term neurological sequelae. Five patients were rechallenged by programmed-cell death 1 monotherapy without recurrence of their neurological immune-related adverse event(s). Neurological immune-related adverse events induced by programmed-cell death 1 or programmed-cell death 1 ligand are rare but are severe with a mortality rate of 8% and long-term sequelae for 53% of patients. Corticosteroids should be started when neurological immunological complications are identified to avoid long-term sequelae. Plaçais et al. report a large case-series of 40 patients presenting with 51 neurologi