{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:04:03Z","timestamp":1779685443688,"version":"3.53.1"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ivonescimab, a novel PD-1\/VEGF bispecific antibody, has shown promising efficacy in advanced lung cancer. Yet severe immune-related adverse events are not well studied outside clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>We report a 72-year-old man with stage IV squamous NSCLC harboring an EGFR mutation and PD-L1 tumor proportion score of 90% who developed persistent fever shortly after first exposure to ivonescimab combined with nab-paclitaxel and carboplatin. His prior treatments included concurrent chemoradiotherapy, osimertinib, the investigational EGFR inhibitor BH-30643, afatinib, and recent gamma knife for cerebellar metastases plus palliative radiotherapy for bone metastases. After cycle 1, he developed persistent high fever with markedly elevated IL-6 and no response to antimicrobials. Corticosteroids brought rapid relief, pointing to an IL-6\u2013mediated process. Re-exposure to ivonescimab triggered a more severe reaction. He then developed sudden polyuria with low urine osmolality and elevated serum osmolality. Brain MRI showed no typical hypophysitis features. Symptoms improved with corticosteroids, tocilizumab, and desmopressin, consistent with probable arginine vasopressin deficiency (AVP-D), possibly secondary to hypophysitis\u2014though pituitary metastasis cannot be ruled out without biopsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ivonescimab can trigger severe IL-6\u2013dominant inflammatory reactions and endocrine toxicity presenting as AVP-D in susceptible patients. Advanced age, EGFR-mutant\/PD-L1-high tumor biology, recent radiotherapy, and Parkinsonism may have contributed to the inflammatory environment, though none can be proven causal in a single case and each deserves prospective study. Early recognition of persistent steroid-responsive fever, serial IL-6 monitoring, thorough endocrine workup, and timely IL-6 blockade are critical.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1836652","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T04:46:00Z","timestamp":1779684360000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Severe IL-6\u2013dominant immune-mediated inflammatory response complicated by probable arginine vasopressin deficiency following ivonescimab-based therapy in advanced EGFR-mutant lung squamous cell carcinoma: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Fang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Oncology, Jiahui International Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linli","family":"Xuan","sequence":"additional","affiliation":[{"name":"Department of Oncology, Jiahui International Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit (ICU), Jiahui International Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01440","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update","volume":"39","author":"Schneider","year":"2021","journal-title":"J Clin Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-011865","article-title":"Consensus-based disease definitions for endocrine immune-related adverse events of immune checkpoint inhibitors","volume":"13","author":"Zhu","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)02722-3","article-title":"Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China","volume":"405","author":"Xiong","year":"2025","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)01848-3","article-title":"Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (HARMONi-6): a randomised, double-blind, phase 3 trial","volume":"406","author":"Chen","year":"2025","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/0284186X.2017.1406668","article-title":"Interleukin-6 as one of the potential 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