Safety of immune checkpoint inhibitor rechallenge after severe immune-related adverse events: a retrospective analysis.

Autor:	Eldani C; Department of Dermatology, Centre Hospitalier Universitaire (CHU) Bordeaux, Bordeaux, France., Kostine M; Department of Rheumatology, CHU Bordeaux, Bordeaux, France., Faure M; Department of Cardiology, CHU Bordeaux, Bordeaux, France., Lazaro E; Department of Internal Medicine, Haut-Leveque, Bordeaux University Hospital, Bordeaux, France., Rigothier C; Department of Nephrology, Transplantation, and Dialysis, Bordeaux University Hospital Center, Bordeaux, France., Hiriart JB; Hepatology Unit, Bordeaux University Hospital, Bordeaux, France., Teulières B; Department of Gastroenterology and Hepatology, Centre Médico-chirurgical Magellan, Hôpital Haut-Lévêque, CHU de Bordeaux, Bordeaux, France., Poullenot F; Department of Gastroenterology and Hepatology, Centre Médico-chirurgical Magellan, Hôpital Haut-Lévêque, CHU de Bordeaux, Bordeaux, France., Haissaguerre M; Department of Endocrinology, University Hospital of Bordeaux, Bordeaux, France., Zysman M; Pulmonary Department, Pôle Cardio-thoracique, CHU de Bordeaux, Bordeaux, France., Veillon R; Pulmonary Department, Pôle Cardio-thoracique, CHU de Bordeaux, Bordeaux, France., Vergnenegre C; Pulmonary Department, Pôle Cardio-thoracique, CHU de Bordeaux, Bordeaux, France., Issa N; Intensive Care Unit and Infectious Disease, University Hospital Centre Bordeaux, Bordeaux, France., Domblides C; Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France., Mary-Prey S; Department of Dermatology, Centre Hospitalier Universitaire (CHU) Bordeaux, Bordeaux, France., Beylot-Barry M; Department of Dermatology, Centre Hospitalier Universitaire (CHU) Bordeaux, Bordeaux, France.; BRIC (BoRdeaux Institute of onCology), Institut National de la Santé et de la Recherche Médicale (INSERM), Univ. Bordeaux, Bordeaux, France., Pham-Ledard A; Department of Dermatology, Centre Hospitalier Universitaire (CHU) Bordeaux, Bordeaux, France.; BRIC (BoRdeaux Institute of onCology), Institut National de la Santé et de la Recherche Médicale (INSERM), Univ. Bordeaux, Bordeaux, France., Dutriaux C; Department of Dermatology, Centre Hospitalier Universitaire (CHU) Bordeaux, Bordeaux, France., Sole G; AOC Referral Center for Neuromuscular Diseases, Neurology and Neuromuscular Diseases Department, FILNEMUS, University Hospitals of Bordeaux, Bordeaux, France., Duval F; AOC Referral Center for Neuromuscular Diseases, Neurology and Neuromuscular Diseases Department, FILNEMUS, University Hospitals of Bordeaux, Bordeaux, France., Gerard E; Department of Dermatology, Centre Hospitalier Universitaire (CHU) Bordeaux, Bordeaux, France.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2024 Jul 08; Vol. 14, pp. 1403658. Date of Electronic Publication: 2024 Jul 08 (Print Publication: 2024).
DOI:	10.3389/fonc.2024.1403658
Abstrakt:	Immune checkpoint inhibitors (ICIs) present clinicians with the challenge of managing immune-related adverse events (irAEs), which can range from mild to severe due to immune system activation 1 . While guidelines recommend discontinuing ICIs for grade 3 partial and all grade 4 irAEs, there is growing interest in rechallenging patients based on oncological outcomes, particularly for cardiovascular and neurological irAEs where data remains scarce 1,2 . We retrospectively evaluated the safety of ICI rechallenge following grade 3-4 irAEs, specifically focusing on cardiovascular and neurological events, in patients discussed at our multidisciplinary immunotoxicity assessment board between 2019 and 2021. Fifteen patients were included, with a median time to severe irAE onset of 49 days. Among them, five patients experienced neurological adverse events (NAEs): aseptic meningitis (3), inflammatory polyradiculoneuropathy (1), and ophthalmoplegia (1), while one patient presented with myocarditis. Of the 15 patients retreated with ICIs after initial severe irAEs, 11 (73%) remained free of subsequent irAEs, two (13%) experienced recurrence of the initial irAE, and two (13%) developed new irAEs distinct from the initial event. The median time to event recurrence was 69 days, occurring no earlier than the initial severe irAE. In the subset analysis focusing on severe cardiovascular and neurological irAEs, rechallenge with ICIs was generally well tolerated. However, one patient treated with anti-PD1 experienced a relapse of grade 2 aseptic meningitis. Overall, our findings suggest that rechallenging with ICIs after severe irAEs, including those affecting the cardiovascular and neurological systems, may be safe, particularly after irAE regression and corticosteroid withdrawal. Competing Interests: EG: congress fees and investigator for BMS and MSD. RV: speakers’ bureau for BMS. SM-P: consultant on boards for BMS. AP-L: congress fees for BMS. CDu: Clinical investigation in trials, congress fees and member of boards for BMS, MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Eldani, Kostine, Faure, Lazaro, Rigothier, Hiriart, Teulières, Poullenot, Haissaguerre, Zysman, Veillon, Vergnenegre, Issa, Domblides, Mary-Prey, Beylot-Barry, Pham-Ledard, Dutriaux, Sole, Duval and Gerard.)
Databáze:	MEDLINE
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