Cytokine Release Syndrome Induced by Combination Therapy With Nivolumab and Ipilimumab in Lower Palpebral Conjunctival Melanoma: A Case Report

Cytokine release syndrome (CRS) induced by immune checkpoint inhibitors (ICIs) is a potentially life-threatening immune-related adverse event (irAE). CRS has been recognized as a complication of chimeric antigen receptor T-cell (CAR-T) therapy and bispecific T-cell engager (BiTE) therapy, but remains exceedingly rare as a complication of ICI therapy. Here, we report a case of CRS that developed after combination therapy with nivolumab and ipilimumab in a woman in her 60s with advanced conjunctival melanoma. The diagnosis was based on the clinical course and imaging findings together with characteristic laboratory abnormalities, including systemic inflammation, hepatic dysfunction, coagulopathy, and marked hyperferritinemia. This case highlights the importance of careful exclusion of infectious and neoplastic diseases for early diagnosis, demonstrates that ICI-related CRS can relapse after initial control, and shows that it may overlap with hemophagocytic lymphohistiocytosis (HLH)-like syndromes. Given the central role of interleukin-6 (IL-6) in CRS, early administration of tocilizumab may contribute to rapid control of inflammation and reduction of steroid exposure.