{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:25:43Z","timestamp":1790717143421,"version":"4.1.0"},"reference-count":27,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"unspecified","delay-in-days":22,"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":[[2026,6,8]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune-related adverse events (irAEs) have been associated with improved overall survival (OS) in patients with cancer treated with immune checkpoint inhibitors (ICIs), as irAEs are thought to signify a potentially robust antitumor immune response. The interplay between irAE subtypes, irAE severity, and oncological outcomes remains understudied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective study of patients with cancer in the US Veteran Health Administration who received first-line or second-line ICI therapy (programmed cell death protein 1, programmed death-ligand 1, cytotoxic T-lymphocyte-associated protein 4, or lymphocyte activation gene 3 inhibitors)\u00b1chemotherapy from 2010 to 2023. Manual chart review was performed on a random sample to ascertain irAEs. The primary outcome was OS, analyzed by irAE status (no irAE vs irAE), severity (steroid-requiring vs non-steroid-requiring), and subtype (thyroid\/cutaneous vs other). To account for immortal time bias, OS was analyzed with multivariable time-dependent Cox regression and 180-day landmark analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 1707 patients, 465 (27.2%) experienced at least one irAE (median onset: 108 days; unadjusted 2-year rate: 38.2% (35%\u201341%)). The occurrence of any-grade irAE was not associated with improved OS (adjusted HR (aHR) 0.87; 95% CI 0.75 to 1.01). Analysis stratified by steroid requirement (n=222\/465 events, 47.7%) showed improved survival with non-steroid-requiring irAE (aHR 0.69, 95%\u2009CI 0.57 to 0.84), whereas steroid-requiring irAEs were associated with a trend toward worse survival (aHR 1.13, 95%\u2009CI 0.92 to 1.38). The non-steroid-requiring irAE subset was enriched for thyroid (45% vs 8%)\u2009and cutaneous (27% vs 16%) toxicities compared with the steroid-requiring group. Exploration of the impact of irAE subtype on OS showed significant survival benefit in patients with thyroid\/cutaneous irAEs (aHR 0.57, 95% CI 0.46 to 0.71)\u2009but not other irAE subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>irAEs are not uniformly associated with improved survival. Favorable outcomes are driven by thyroid-related and skin-related, non-steroid-requiring irAEs, suggesting shared biological mechanisms underlying organ-specific autoimmunity and antitumor immune response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014622","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:55:15Z","timestamp":1782237315000},"page":"e014622","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Heterogeneous survival impact of immune-related adverse events in US veterans"],"prefix":"10.1136","volume":"14","author":[{"given":"Sadiq","family":"Rehmani","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4003-8535","authenticated-orcid":false,"given":"Luke Michael","family":"Higgins","sequence":"additional","affiliation":[{"name":"Radiation Oncology, University of Michigan Medicine, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Brinzevich","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Falvello","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garth W","family":"Strohbehn","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA"},{"name":"Division of Oncology, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Dykstra","sequence":"additional","affiliation":[{"name":"Radiation Oncology, University of Michigan Medicine, Ann Arbor, Michigan, USA"},{"name":"Department of Radiation Oncology, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Elliott","sequence":"additional","affiliation":[{"name":"Radiation Oncology, University of Michigan Medicine, Ann Arbor, Michigan, USA"},{"name":"Department of Radiation Oncology, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nithya","family":"Ramnath","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA"},{"name":"Division of Oncology, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex K","family":"Bryant","sequence":"additional","affiliation":[{"name":"Radiation Oncology, University of Michigan Medicine, Ann Arbor, Michigan, USA"},{"name":"Department of Radiation Oncology, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"2026062310551316000_14.6.e014622.1","doi-asserted-by":"crossref","unstructured":"Zhao B , Zhao H , Zhao J . 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