Severe IL-6–dominant 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

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Background: 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. Case presentation: 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-mediated 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-though pituitary metastasis cannot be ruled out without biopsy. Conclusions: Ivonescimab can trigger severe IL-6-dominant 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.

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