Clinical and Proteomic Insights into a Cytokine Release Syndrome Triggered by Tebentafusp in a Metastatic Uveal Melanoma Patient: Case Report.

Uveal melanoma is the most common primary intraocular cancer in adults; however, it remains rare. Despite its rarity, metastatic uveal melanoma poses significant treatment challenges. Tebentafusp, a T-cell receptor-bispecific molecule targeting glycoprotein 100 and CD3, has shown substantial survival benefits for HLA-A*02:01 positive patients. A notable complication associated with tebentafusp and similar immunotherapies is cytokine release syndrome (CRS), occurring in nearly 90% of tebentafusp-treated patients. Although typically mild, severe CRS (grade 3) affects around 1% of patients. The unpredictable nature of CRS complicates patient management during treatment. Monitoring cytokine levels, as key indicators of inflammation, may therefore be crucial for understanding and managing CRS. Advanced proteomic technologies enable the simultaneous measurement of multiple cytokines, providing a comprehensive view of inflammatory responses. In this case, a patient with metastatic uveal melanoma developed CRS after tebentafusp treatment. A proteomic analysis tracked the cytokine changes from baseline to post-treatment, revealing significant elevations in inflammatory markers. These findings suggest potential strategies for more personalized CRS management in similar therapies.