Impact on survival of severe immuno-related adverse events in deficient mismatch repair/microsatellite instable-high digestive cancers treated with immunotherapy

作者：David Tougeron, Charles Kauffmann, Margherita Ambrosini, Olayidé Boussari, Sara Lonardi, Frank A. Sinicrope, Marwan Fakih, Michael J. Overman, Elena Élez, Anthony Turpin, Marie Decraecker, Antoine Hollebecque, Simon Pernot, Thibault Mazard, Marie Dutherage, Romain Cohen, Francesco Sclafani, Mohamed Ben Abdelghani, Thomas Aparicio, Clélia Coutzac, Vincent Hautefeuille, Marie Muller, Chiara Cremolini, Rosine Guimbaud, Julien Taı̈eb, Filippo Pietrantonio, Raphaël Olivier, Emily Alouani · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2026 · DOI：10.1136/jitc-2026-015273 · 研究领域：Genetic factors in colorectal cancer、Cancer Immunotherapy and Biomarkers、Multiple and Secondary Primary Cancers

BACKGROUND: Deficient DNA mismatch repair/microsatellite instability-high (dMMR/MSI-H) cancers are very sensitive to immune checkpoint inhibitors (ICIs), yet their use is frequently complicated by immune-related adverse events (irAEs). Our study analyzed the impact of grade ≥3 irAEs (immune-related severe adverse events (irSAEs)) on survival in patients with dMMR/MSI-H digestive cancers treated with ICIs. METHODS: We conducted an international, multicenter, ambispective study involving 1,175 patients from 34 centers. The primary endpoint was the correlation between the occurrence of irSAEs and progression-free survival (PFS). Secondary endpoints included factors associated with irSAEs, correlation between irSAEs and overall response rate (ORR) and overall survival (OS). Prespecified landmark and time-dependent survival models were used to account for the time to irSAE occurrence. RESULTS: Among 1,175 patients treated with ICIs for digestive cancers, 49.1% were female, median age was 66.9 years (IQR 53.7-77.3) and 82.9% had colorectal cancer. Overall, 382 patients (32.5%) had an irAE, including 117 (10.0%) irSAEs. Median time to irSAEs occurrence was 3.78 months (IQR 1.97-7.62). The most frequent irSAEs were gastrointestinal (3.4%), hepatic (1.8%) and dermatologic (1.0%). The only factor associated with irSAEs was the use of an ICI combination versus monotherapy (20.0% vs 11.4%, p=0.03). Among patients with irSAEs, 71.5% received oral and 29.8% intravenous corticosteroids, and...