{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:39:04Z","timestamp":1792809544818,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K18657"],"award-info":[{"award-number":["25K18657"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Immune\u2010related adverse events (irAEs) frequently occur during combination immune checkpoint inhibition. However, their prognostic impact may vary according to organ involvement and severity. In this study, we exploratorily evaluated whether severe non\u2010endocrine irAEs represent a temporally distinct and prognostically unfavorable clinical phenotype in patients with metastatic renal cell carcinoma (mRCC) treated with ipilimumab plus nivolumab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>We analyzed 63 patients with mRCC treated with ipilimumab plus nivolumab who were followed for at least 5\u2009years. Patients were categorized into non\u2010irAE, non\u2010severe\u2009+\u2009severe endocrine irAE, and severe non\u2010endocrine irAE groups. Overall survival (OS) was assessed. Multistate modeling was used to evaluate the transitions between treatment, irAE occurrence, and death. Landmark analyses were performed at 8 and 12\u2009weeks to address immortal time bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The severe non\u2010endocrine irAE group was associated with inferior OS. The multistate analysis revealed a potentially increased risk of direct transition from ipilimumab plus nivolumab to death in the severe non\u2010endocrine irAE group. A significantly higher proportion of patients in the severe non\u2010endocrine irAE group experienced irAEs within 30\u2009days. No significant association was observed in the 8\u2010 and 12\u2010week landmark analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this exploratory retrospective study, severe non\u2010endocrine irAEs showed an association with early onset and potentially unfavorable clinical outcomes in patients with mRCC receiving ipilimumab plus nivolumab. Given the limited sample size, these findings should be interpreted cautiously and require confirmation in larger independent cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72410","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:42:23Z","timestamp":1792464143000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Organ\u2010Specific Severe Immune\u2010Related Adverse Events on Long\u2010Term Survival and Treatment Transitions in Metastatic Renal Cell Carcinoma: A 5\u2010Year Multicenter Multistate Analysis"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1830-7452","authenticated-orcid":false,"given":"Yoshihiko","family":"Tasaki","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmaceutics Nagoya City University Graduate School of Medical Sciences  Nagoya Aichi 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