Efficacy of immunotherapy and sequencing of checkpoint inhibition for metastatic ocular melanoma.

Abstract

e21526 Background: Ocular melanoma (OM) is the most common intraocular tumor in adults. However, it is still rare as compared to other subtypes of melanoma. Treatment of primary OM is certainly successful, but most therapies assessed in treatment of metastatic OM have not shown promise. Immunotherapy (IO), which has otherwise held prospect for durable remissions in other metastatic melanoma has shown no evidence in metastatic OM. Our study aims at narrowing the gap in knowledge in the treatment of OM with IO. Methods: We conducted a retrospective cohort study of patients with metastatic OM treated during the period 2017-2021 at the University of Louisville. Patients aged 18 years or more with treatment-naïve metastatic (Stage IV) OM were included. Data was censored according to date of last recorded clinical follow up or death. The primary outcome of interest was overall survival (OS). Subgroup analysis was done to examine survival based on initial treatment with dual versus single checkpoint inhibition. After progression on initial therapy, patients previously on dual inhibition went on to receive single inhibition, and vice versa. Kaplan-Meier survival analyses were generated using all-cause mortality as the competing outcome event and log-rank testing to evaluate differences between groups with alpha set at 0.05 for significance. Results: A total of 21 patients with Stage IV OM were identified with 4 excluded due to lack of data. The majority were male (10/17) and median age was 66 years, ranging from 30 to 89 years. More than half (10/17) received dual checkpoint inhibition as initial IO, with ipilimumab and nivolumab. The remainder received pembrolizumab or Nivolumab monotherapy (7/17). IO was well tolerated with no treatment related mortality and incidence of immune-related adverse effects similar to cutaneous melanoma. The median follow-up time overall was 56 months using the reverse Kaplan-Meier method with a median OS of 15 months. Estimated 2-year OS was 41%. No significant difference was found between single and dual checkpoint inhibition as the initial treatment regimen. Conclusions: While IO has markedly improved survival in advanced melanomas, OM continues to have inferior survival. Consistent with the literature by Zimmer et al, survival in this cohort is better than that reported with ipilimumab monotherapy. The median survival of 15 months is consistent with that reported by Heppt et al in the German multicenter study. IO for Stage IV OM was well tolerated, resulting in median survival of 15 months and 2-year OS of 41%. There was no survival advantage to initial treatment with single versus dual checkpoint inhibition, allowing for crossover at progression. Further research with novel agents and enrollment in clinical trials are needed in ocular melanoma.