Associations between patient and disease characteristics and severe adverse events during immune checkpoint inhibitor treatment: An observational study. (October 2022)

• Record Type: Journal Article
• Authors: Basak, Edwin A.; Vermeer, Niels S.; de Joode, Karlijn; Hurkmans, Daan P.; Velthuis, Dorian E.M.; Oomen-de Hoop, Esther; Schreurs, Marco W.J.; Bins, Sander; Koolen, Stijn L.W.; Debets, Reno; van der Veldt, Astrid A.M.; Aerts, Joachim G.J.V.; Joosse, Arjen; Mathijssen, Ron H.J.
• Is Part Of: European journal of cancer. Volume 174(2022)
• Page Start: 113
• Page End: 120
• Publication Date: 2022-10
• Subjects: Anti-PD-1 -- Anti-CTLA-4 -- Severe immune-related adverse events -- Melanoma -- NSCLC; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2022.07.015
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Aim: With increasing use of immune checkpoint inhibitors (ICIs) more patients will develop severe and potentially life-threatening immune-related adverse events (irAEs). So far, predictive models for the occurrence of grade ≥3 irAEs are lacking. Therefore, we analysed associations between patient and disease characteristics, and the occurrence of grade ≥3 irAEs. Methods: Patients with cancer who were treated with anti-PD-1 (+/−anti-CTLA-4) between July 2015 and February 2020, and who were prospectively included in the MULTOMAB-trial, were eligible for this cohort study. Time to and occurrence of grade ≥3 irAEs according to CTCAE v5.0 were retrospectively registered. The associations between patient and disease characteristics and irAE occurrence were analysed using the competing risk cox-regression model of Fine and Gray. Analyses were performed separately in patients treated with monotherapy (anti-PD-1) and combination therapy (anti-PD-1 + anti-CTLA-4). Subgroup analyses were performed in tumour types with the highest number of patients; melanoma and NSCLC. Results: Out of 641 patients, 106 patients (17%) experienced grade ≥3 irAEs. None of the analysed factors were associated with grade ≥3 irAE occurrence in the monotherapy (n = 550) or the combination therapy (n = 91) groups, nor in the subgroup analyses. Of interest, none of the patients with NSCLC with a WHO performance status of 0 (n = 34) experienced grade ≥3 irAEs. Most common NSCLC histology types were adenocarcinoma (n = 99/55%) and squamous cell carcinoma (n = 39/22%). Concluding statement: This study shows that patient and disease characteristics are not able to predict the occurrence of serious AEs in patients treated with ICIs. Highlights: 12% of patients receiving anti-PD-1 monotherapy experienced grade ≥3 toxicities. 44% of patients receiving anti-PD-1 + CTLA-4 therapy experienced grade ≥3 toxicities. No clinical factor was associated with toxicities during anti-PD-1 (+CTLA4) therapy. This was found across tumour types, as well as in melanoma and NSCLC patients.