Retrospective multicenter analysis of real-life toxicity and outcome of ipilimumab and nivolumab in metastatic uveal melanoma
Background: Uveal melanoma (UM) is the most common primary ocular malignancy with a high rate of metastases. While immune checkpoint inhibitors (ICIs), including ipilimumab and nivolumab (ipi+nivo), have shown efficacy in metastatic cutaneous melanoma, their success in metastatic UM (MUM) remains limited. This study evaluates toxicity and outcomes of ipi+nivo in the largest, multicenter MUM cohort.
Methods: We analyzed 131 MUM patients treated with ipi+nivo from 2016-2024 across five international centers. Rates of toxicity, response, and survival outcomes were assessed.
Results: Among 131 patients, 37.4% of patients received four cycles of ipi+nivo. The most common reason for ipi+nivo discontinuation (31.3%) was toxicity. Of all treated patients, 80.2% experienced immune-related adverse events (irAEs). The overall response rate (ORR) was 16.4%, and the disease control rate (DCR) was 43.4%. Progression-free survival (PFS) was three months, and the median overall survival (OS) was 18 months. Patients receiving ipi+nivo as second-line therapy had lower ORR compared to patients who received ipi+nivo as first-line therapy (p = 0.04). Patients with exclusively extrahepatic metastases had a better ORR and OS compared to those with hepatic or mixed metastases (p = 0.02, p = 0.02, respectively). 20.6% of patients developed eosinophilia during treatment, which was associated with improved median OS (24 months vs. 15 months, p = 0.02).
Conclusions: Ipi+nivo shows moderate efficacy and clinically relevant toxicities in patients with MUM. Eosinophilia is a potential prognostic biomarker, that merits further investigation.
Keywords: eosinophilia; immune checkpoint inhibitors; immune-related adverse events; uveal melanoma.
