Severe Multisystem Toxicity from Combination Ipilimumab and Nivolumab in Metastatic Melanoma: A Case Report.

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy by enhancing antitumor immunity. Despite their remarkable efficacy in malignancies, particularly metastatic melanomas, the use of ICIs have been linked to life-threatening immune-related adverse events (irAEs) affecting several organ systems. Combination therapy with ipilimumab and nivolumab increases both efficacy and the risk of severe irAEs. We report a rare case of metastatic melanoma treated with combination ipilimumab and nivolumab, complicated by multisystem irAEs. The patient developed hepatitis, cholangitis, ocular toxicity, and neurologic progression, highlighting the severity and complexity of immune-mediated toxicities following dual checkpoint blockade. This case underscores the potential for severe, multisystem irAEs with combination ICIs and the need for vigilant monitoring, early recognition, and multidisciplinary management. Understanding the mechanisms and predictors of these toxicities is essential to optimize treatment outcomes while minimizing life-threatening complications.