Impact of immunosuppressive agents on the management of immune-related adverse events of immune checkpoint blockers

Pierre-Louis Cariou; Cédric Pobel; Jean-Marie Michot; François-Xavier Danlos; Benjamin Besse; Franck Carbonnel; Xavier Mariette; Aurélien Marabelle; Sabine Messayke; Caroline Robert; Emilie Routier; Nicolas Noël; Olivier Lambotte

doi:10.1016/j.ejca.2024.114065

Impact of immunosuppressive agents on the management of immune-related adverse events of immune checkpoint blockers

Eur J Cancer. 2024 Apr 14:204:114065. doi: 10.1016/j.ejca.2024.114065. Online ahead of print.

Affiliations

¹ Université Paris Saclay, AP-HP, Hôpital de Bicêtre, Department of Internal Medicine, UMR 1184, CEA INSERM, FHU CARE, Le Kremlin Bicêtre, France.
² Drug Development Department (DITEP), Gustave Roussy, 94805 Villejuif, France.
³ Department of Cancer Medicine, Gustave Roussy, Villejuif, France.
⁴ AP-HP, Department of Gastroenterology, University Hospital of Bicêtre, Paris Sud University, FHU CARE, 78 Rue du General Leclerc, 94270 Le Kremlin-Bicetre, France.
⁵ Université Paris-Saclay, AP-HP, Hôpital Bicêtre, Rheumatology Department, INSERM UMR 1184, FHU CARE, Paris, Le Kremlin Bicêtre, France.
⁶ Gustave Roussy - Paris-Saclay University, Pharmacovigilance Unit, 94800 Villejuif, France.
⁷ Dermatology Service, Department of Medicine, Gustave Roussy and Paris-Saclay University, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
⁸ Université Paris Saclay, AP-HP, Hôpital de Bicêtre, Department of Internal Medicine, UMR 1184, CEA INSERM, FHU CARE, Le Kremlin Bicêtre, France. Electronic address: olivier.lambotte@aphp.fr.

PMID: 38643707
DOI: 10.1016/j.ejca.2024.114065

Abstract

Background: Immune checkpoint blockers (ICBs) can induce immune-related adverse events (irAEs) whose management is based on expert opinion and may require the prescription of steroids and/or immunosuppressants (ISs). Recent data suggest that these treatments can reduce the effectiveness of ICBs.

Objective: To investigate the relationship between the use of steroids and/or ISs and overall survival (OS) and progression-free survival (PFS) among ICB-treated patients with an irAE.

Methods: We prospectively collected data from the medical records of patients with solid tumors or lymphoma in the French REISAMIC cohort and who had been treated with ICBs between June 2014 and June 2020.

Results: 184 ICB-treated patients experienced at least one Common Terminology Criteria for Adverse Events grade ≥ 2 irAE. 107 (58.2%) were treated with steroids alone, 20 (10.9%) with steroids plus IS, 57 (31.0%) not received steroids or IS. The median OS was significantly shorter for patients treated with steroids alone (25.2 months [95% confidence interval (CI): 22.3-32.4] than for patients treated without steroids or IS (63 months [95%CI: 40.4-NA]) and those receiving an IS with steroids (53.4 months [95%CI: 47.3-NA]) (p < 0.001). The median PFS was significantly shorter for patients treated with steroids alone (17.0 months [95%CI: 11.7-22.9]) than for patients treated without steroids or IS (33.9 months [95%CI: 18.0-NA]) and those receiving an IS with steroids (41.1 months [95%CI: 26.2-NA]) (p = 0.006). There were no significant intergroup differences in the hospital admission and infection rates.

Conclusion: In a prospective cohort of ICB-treated patients, the use of IS was not associated with worse OS or PFS, contrasting with the use of steroids for the management of irAEs.

Keywords: Corticosteroid; Immune checkpoint blocker; Immune-related adverse events; Immunosuppressant agent.