Durable stable disease and immune activation in metastatic uveal melanoma treated with tebentafusp: case report

Metastatic uveal melanoma (mUM) is a rare, aggressive malignancy with limited therapeutic options in the metastatic setting. Tebentafusp (IMCgp100) is an immune-mobilizing monoclonal T cell receptor against cancer (ImmTAC), targeting gp100 in HLA-A*0201+ patients. Tebentafusp has demonstrated an overall survival (OS) benefit in clinical trials, usually without marked radiographic tumor regression. We describe a mUM patient who was treated with tebentafusp for more than two years and achieved durable stable disease on imaging but passed away due to sudden cardiac death. Autopsy examination revealed extensive tumor necrosis and dense immune cell infiltration within metastatic liver lesions with minimally viable tumor, providing direct evidence of robust immune activation in the tumor microenvironment. This case highlights the potential for T cell bispecifics to induce profound anti-tumor effects that are not fully captured by conventional radiographic assessment, underscoring the need for integrated clinical, pathologic, and imaging evaluation in this setting.