Evaluation of the modified immune prognostic index to prognosticate outcomes in metastatic uveal melanoma patients treated with immune checkpoint inhibitors

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.

Efficacy and Safety of Immune Checkpoint Blockades in the Treatment of Ocular Melanoma: A Systematic Review and Meta-Analysis

“…Our meta-analysis also demonstrated the favorable outcome of disease control rate (DCR) following ICB treatment (Figure S4). Vecchio et al reported immune-related disease control for 36% of patients with metastatic mucosal melanoma, and in most cases, the improved DCR was attributed to SD rather than to a significant reduction in the tumor burden (36). Sander et al (36) showed that beneficial ORR was notable for metastatic UM patients who achieved a PR, and patients having attained either a PR or SD had an improved DCR (36).…”

“…Vecchio et al reported immune-related disease control for 36% of patients with metastatic mucosal melanoma, and in most cases, the improved DCR was attributed to SD rather than to a significant reduction in the tumor burden (36). Sander et al (36) showed that beneficial ORR was notable for metastatic UM patients who achieved a PR, and patients having attained either a PR or SD had an improved DCR (36). Moreover, though a modified immune prognostic index (IPI) status might be used to predict a survival benefit from ICB treatment, the IPI score was not found to be associated with ORR and DCR.…”

“…Vecchio et al. reported immune-related disease control for 36% of patients with metastatic mucosal melanoma, and in most cases, the improved DCR was attributed to SD rather than to a significant reduction in the tumor burden ( 36 ). Sander et al.…”

“…Sander et al. ( 36 ) showed that beneficial ORR was notable for metastatic UM patients who achieved a PR, and patients having attained either a PR or SD had an improved DCR ( 36 ). Moreover, though a modified immune prognostic index (IPI) status might be used to predict a survival benefit from ICB treatment, the IPI score was not found to be associated with ORR and DCR.…”

“…Table 1 describes the characteristics of the 16 eligible articles (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) consisting of 13 cohort and 3 single-arm studies. A total of 848 ocular melanoma patients were enrolled, with an age range of 16-65 years.…”