{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:33:48Z","timestamp":1791999228540,"version":"4.4.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ipilimumab plus nivolumab (Ipi+Nivo) has become a standard therapy for advanced non-small cell lung cancer (NSCLC), yet severe organ-specific toxicities remain inadequately characterized. This study aimed to characterize severe renal and pancreatic toxicities associated with Ipi+Nivo combination therapy versus nivolumab monotherapy in NSCLC patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed the FDA Adverse Event Reporting System (FAERS) database from 2004 Q1 to 2025 Q2. Disproportionality analysis using reporting odds ratio (ROR) and information component (IC) identified safety signals. Time-to-onset and clinical severity were compared between treatment groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 2,292 reports, combination therapy demonstrated significant disproportionality signals for glomerular-predominant renal injury, including glomerulonephritis minimal lesion (ROR = 78.62, IC025 = 2.096), nephrotic syndrome (ROR = 37.25, IC025 = 1.914), and glomerulosclerosis (ROR = 61.79, IC025 = 2.015). Pancreatic toxicity showed strong signals (ROR = 61.79, IC025 = 2.015). Additional renal signals included nephritis (ROR = 24.99, IC025 = 1.832) and renal failure (ROR = 2.99, IC025 = 0.499). Among 447 combination therapy reports, 39 renal events and 23 pancreatic events were identified, compared to 114 and 48 events respectively in 1,814 monotherapy reports. Median time-to-onset was 73 days for renal events and 84 days for pancreatic events in the combination group. Co-reported renal and pancreatic events were infrequent at the report level (2 of 60 combination therapy reports with renal and\/or pancreatic events), and serious clinical outcomes including death and hospitalization were prevalent in both groups without statistically significant between-group differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ipi+Nivo combination therapy is associated with prominent glomerular-predominant renal injury and pancreatic toxicity signals, potentially reflecting distinct immunological mechanisms whereby CTLA-4-dependent disruption of B-cell tolerance may predispose to glomerular injury while PD-1-mediated release of T-cell cytotoxicity may preferentially target pancreatic islets. These findings suggest the need for enhanced clinical vigilance and tailored monitoring strategies beyond conventional acute interstitial nephritis surveillance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1854177","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:51:29Z","timestamp":1781671889000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Severe renal and pancreatic toxicities associated with ipilimumab and nivolumab combination therapy in non-small cell lung cancer: a pharmacovigilance analysis of the FDA adverse event reporting system"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiongrui","family":"Cao","sequence":"first","affiliation":[{"name":"North Sichuan Medical College","place":["Nanchong, Sichuan, China"]},{"name":"Dali University","place":["Dali, Yunnan, China"]},{"name":"Department of Oncology, Panzhihua Central Hospital","place":["Panzhihua, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Peng","sequence":"additional","affiliation":[{"name":"North Sichuan Medical College","place":["Nanchong, Sichuan, China"]},{"name":"Department of Oncology, Panzhihua Central Hospital","place":["Panzhihua, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yang","sequence":"additional","affiliation":[{"name":"North Sichuan Medical College","place":["Nanchong, Sichuan, China"]},{"name":"Department of Oncology, Panzhihua Central Hospital","place":["Panzhihua, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Oncology, Panzhihua Central Hospital","place":["Panzhihua, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Oncology, Panzhihua Central Hospital","place":["Panzhihua, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifa","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Panzhihua Central Hospital","place":["Panzhihua, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Oncology, Panzhihua Central Hospital","place":["Panzhihua, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Oncology, Panzhihua Central Hospital","place":["Panzhihua, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Panzhihua Central Hospital","place":["Panzhihua, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2024.102693","article-title":"Global burden of lung cancer in 2022 and projections to 2050: Incidence and mortality estimates from GLOBOCAN","volume":"93","author":"Zhou","year":"2024","journal-title":"Cancer Epidemiol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.4932","article-title":"Update of incidence, prevalence, survival, and initial treatment in patients with non-small cell lung cancer in the US","volume":"7","author":"Ganti","year":"2021","journal-title":"JAMA 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