Combination of Immune Checkpoint Inhibitors and Liver-Specific Therapies in Liver-Metastatic Uveal Melanoma: Can We Thus Overcome Its High Resistance?

SIMPLE SUMMARY: Immune checkpoint inhibitors (ICI) have failed to overcome the high therapy resistance of Metastatic Uveal Melanoma (MUM) in contrast to the dramatic benefits of immunotherapy seen in many other tumor entities. Considering the poor clinical outcome and survival rates of MUM, the urgent need of new therapeutic approaches becomes apparent. This retrospective single-center cohort study of patients with liver-metastatic UM aims to investigate whether the combination of ICI and liver-directed therapies may improve the activity of immunotherapy against this highly malignant cancer. Our results demonstrate a response to MUM resistance to immunotherapy by combining liver-directed therapies and ICI, leading to improvement of overall survival (OS). ABSTRACT: Uveal Melanoma (UM) is a rare disease; however, it is the most common primary intraocular malignant tumor in adults. Hematogenous metastasis, occurring in up to 50% of cases, mainly to the liver (90%), is associated with poor clinical course and treatment failure. In contrast to dramatic benefits of immunotherapy in many tumor entities, as seen in cutaneous melanoma, immune checkpoint inhibitors (ICI) do not achieve comparable results in Metastatic UM (MUM). The aim of this study was to investigate whether the combination of ICI with liver-directed therapies provides a potential survival benefit for those affected. This retrospective, single-center study, including n = 45 patients with MUM, compared the effect of combining ICI with liver-directed therapy (“Cohort 1”) with respect to standard therapies (“Cohort 2”) on overall survival (OS). Our results revealed a significant survival difference between Cohort 1 (median OS 22.5 months) and Cohort 2 (median OS 11.4 months), indicating that this combination may enhance the efficacy of immunotherapy and thus provide a survival benefit. There is an urgent need for randomized, prospective trials addressing the combination of liver-directed therapies and various strategies of immunotherapy (such as ICI; IMCgp100; personalized vaccines) in order to establish regimens which finally improve the prognosis of patients with MUM.