Abstract
BACKGROUND: Metastatic uveal melanoma (MUM) is associated with poor survival and inferior response to immune checkpoint inhibitor (ICI) therapy when compared with metastatic cutaneous melanoma. Currently, prognostic biomarkers are lacking to guide treatment decisions. PATIENTS AND METHODS: We conducted a multicenter, retrospective cohort study using a centralized, province-wide cancer database in Alberta, Canada. We identified 37 patients with histologically confirmed MUM who received at least one dose of single-agent pembrolizumab or nivolumab, or combination therapy nivolumab and ipilimumab. A modified immune prognostic index (IPI), based on the previously reported lung immune prognostic index, was used to stratify patients into favorable and poor IPI groups. Survival analyses were conducted using the Kaplan-Meier method and Cox proportional hazards models, adjusting for baseline age (≥60) and ECOG performance status, to assess the associations between IPI and overall survival (OS). Time to treatment failure (TTF) was also assessed using the Kaplan-Meier method. The association between IPI and objective response rate was examined using chi-squared tests. Logistic regression was used to determine the association between IPI and immune-related adverse events (irAEs). RESULTS: Median OS was 15.6 (range 0.6-57.6) months with 45.9% 1-year survival rate at a median follow-up of 11.8 months. We found that a favorable IPI was significantly associated with OS [median 30.5 (12.0-not reached) months in the favorable IPI group compared with 4.6 (2.1-16.0) months in the poor IPI group (p = 0.001)] (HR=4.81, 95% CI; 1.64-14.10, p = 0.004), TTF [median 5.1 (95% CI; 2.1-10.4) months in the favorable IPI group compared with 3.7 (95% CI; 1.4-6.4) months in the poor IPI group (p = 0.0191)], and irAE (HR=6.67, 95% CI; 1.32-33.69, p = 0.0220). CONCLUSIONS: The modified IPI may be a useful tool in clinical practice for identifying MUM patients who are more likely to experience irAEs and realize a survival benefit from ICI treatment.