{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T14:05:01Z","timestamp":1784901901346,"version":"3.55.0"},"reference-count":45,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"unspecified","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,7,3]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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 \u22653 irAEs (immune-related severe adverse events (irSAEs)) on survival in patients with dMMR\/MSI-H digestive cancers treated with ICIs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 1,175 patients treated with ICIs for digestive cancers, 49.1% were female, median age was 66.9 years (IQR 53.7\u201377.3) 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\u20137.62). 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 15.7% immunosuppressive agents. Overall, in 26.9% of patients, ICIs were resumed following irSAEs, with an irAE recurrence rate of 57.1%. irSAE was associated with a better ORR (48.6% vs 34.6%, p&lt;0.0001). The multivariable Cox model revealed that irSAE as a time-dependent variable was not associated with better PFS (HR=1.280 (95% CI 0.898 to 1.824), p=0.172) or OS (HR=1.043 (95% CI 0.712 to 1.528), p=0.828). Likewise, landmark analysis at 3 months and 6 months also showed that irSAEs were not associated with better PFS or OS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The occurrence of irSAE was not independently associated with better survival in patients with dMMR\/MSI-H digestive cancers treated with ICIs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2026-015273","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:20:36Z","timestamp":1784899236000},"page":"e015273","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Impact on survival of severe immuno-related adverse events in deficient mismatch repair\/microsatellite instable-high digestive cancers treated with immunotherapy"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8065-9635","authenticated-orcid":false,"given":"David","family":"Tougeron","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Poitiers University Hospital, Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Kauffmann","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Poitiers University Hospital, Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4131-2409","authenticated-orcid":false,"given":"Margherita","family":"Ambrosini","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Foundation IRCCS National Cancer Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olayide","family":"Boussari","sequence":"additional","affiliation":[{"name":"Department of Methodology, Federation Francophone de Cancerologie Digestive, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7593-8138","authenticated-orcid":false,"given":"Sara","family":"Lonardi","sequence":"additional","affiliation":[{"name":"Oncologia Medica, Istituto Oncologico Veneto Istituto di Ricovero e Cura a Carattere Scientifico, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank A","family":"Sinicrope","sequence":"additional","affiliation":[{"name":"Department of Oncology, Mayo Clinc, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6554-5488","authenticated-orcid":false,"given":"Marwan","family":"Fakih","sequence":"additional","affiliation":[{"name":"Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center Duarte, Duarte, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5377-135X","authenticated-orcid":false,"given":"Michael J","family":"Overman","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4653-6324","authenticated-orcid":false,"given":"Elena","family":"Elez","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Vall d\u2019Hebron Institute of Oncology, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Turpin","sequence":"additional","affiliation":[{"name":"Lille University, UMR9020 CNRS-U1366 INSERM, CHU de Lille, Medical Oncology Department, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Decraecker","sequence":"additional","affiliation":[{"name":"Department of Hepato-gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Hollebecque","sequence":"additional","affiliation":[{"name":"University of Lorraine, Department of Hepato-Gastroenterology and Digestive Oncology, Nancy University Hospital, Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Pernot","sequence":"additional","affiliation":[{"name":"Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibault","family":"Mazard","sequence":"additional","affiliation":[{"name":"Digestive Medical Oncology Department, Unviersity Hospital of Toulouse, Toulouse, 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