Metastatic uveal melanoma (mUM) is associated with poor prognosis. Ipilimumab/nivolumab has shown antitumor efficacy in phase II studies. Tebentafusp resulted in longer overall survival (OS) compared to investigator`s choice in a phase III study. We sought to describe the radiological response patterns of mUM patients treated with immunotherapy. Patients with mUM treated with ipilimumab/nivolumab and tebentafusp between July 2018 and December 2022, with available radiological assessment per RECISTv1.1 and/or imPERCIST5, were retrospectively identified and included. Progression-free survival (PFS) and OS rates, liver-specific response and pathological assessment in available liver biopsies were evaluated. In the ipilimumab/nivolumab group, median PFS (mPFS) was 2.9 months (95% CI 2.2–28.6) and mOS 28.9 months (95% CI 12.7-NR). Complete (CMR) and partial (PMR) metabolic response per imPERCIST5, and partial response (PR) per RECISTv1.1 were associated with longer PFS and OS by trend, compared to morphologically and metabolically stable or progressive disease. In the tebentafusp group, mPFS was 2.7 months (95% CI 2.2–3) and mOS 18.6 months (95% CI 11.5-NR). PMR and PR were associated with longer PFS by trend. In both treatments, the overall treatment response was associated with the radiological response at the liver site. In available liver tumor biopsies, differences in pathological and radiological responses were noted. ImPERCIST5 and RECIST v1.1 are valuable tools in the radiological response assessment, but both methods display limitations. Accurate biomarkers to stratify patients at risk for disease progression and future translational studies to investigate mechanisms of response and resistance are required.

Background Metastatic uveal melanoma (mUM) is associated with poor prognosis. Treatment with ipilimumab/nivolumab has shown antitumor efficacy. Tebentafusp resulted in longer overall survival (OS) compared to investigator`s choice in a phase III study. The aim of this study is to describe the radiological response patterns with both treatments in association with the treatment outcome. Methods Patients with mUM treated with ipilimumab/nivolumab or tebentafusp with available radiological assessment per RECISTv1.1 and/or imPERCIST5. Disease outcome, landmark progression-free survival (PFS) and OS were reported. The same criteria were used to assess the liver-specific response. Results 14 patients were treated with ipilimumab/nivolumab; treatment efficacy for best overall response (BOR) per RECIST v1.1 and imPERCIST5 was similar for the PFS (p=0.37 and p=0.23) and OS (p=0.14 and p=0.23). Patients with complete metabolic response (CMR), partial metabolic response (PMR) and partial response (PR) had longer PFS by trend. Treatment efficacy at the liver was concordant with the overall treatment efficacy for the PFS and OS. 22 patients were treated with tebentafusp; BOR per imPERCIST5 and RECISTv1.1 did not differ for the PFS (p=0.48 and p=0.21, respectively) and OS (p=0.63 and p=0.32, respectively). The hepatic treatment efficacy was concordant with the overall treatment efficacy. Patients with liver SD as best response showed a significant OS benefit (p=0.045). Conclusion Comprehensive radiological response evaluation with both RECIST v1.1 and imPERCIST5 can synergistically provide with an accurate assessment of immunotherapy efficacy in mUM, but both methods display limitations. Further studies to investigate the mechanisms of response and resistance are required.