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.
Bibliographical noteFunding Information:
EAB, NSV, KdJ, DPH, DEMV, EOH, MWJS, SB, SLWK declares having no relevant conflict of interest. RD has received research support from MSD and Bayer, personal fees from Bluebird Bio, Genticel, other support from Pan Cancer T outside the submitted work (all paid to the Erasmus MC Cancer Institute), as well as European patent application no's. 21152822.9 and 21184727.2. AAMvdV declares having received consultancy fees (paid to the institute) from BMS, MSD, Merck, Eisai, Ipsen, Pfizer, Pierre Fabre, Novartis, Roche, Sanofi. JGJVA declares having received consulting fees from MSD, BMS, Boehringer Ingelheim, Amphera, Eli-Lilly, Takeda, Bayer, Roche, Astra Zeneca, BIOCAD, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from MSD, BMS, Boehringer Ingelheim, Amphera, Eli-Lilly, Takeda, Bayer, Roche, Astra Zeneca, BIOCAD, having patents planned, issued or pending regarding biomarkers for immunotherapy, allogenic tumour cell lysates. AJ declares having received support for attending meetings and/or travel from Ipsen. RHJM declares having received grants or contracts (paid to the institute) from Astellas, Bayer, Cristal Therapeutics, Novartis, Pamgene, Pfizer, Roche, Sanofi, Servier.
© 2022 The Author(s)