Poor Response to Checkpoint Immunotherapy in Uveal Melanoma Highlights the Persistent Need for Innovative Regional Therapy Approaches to Manage Liver Metastases

SIMPLE SUMMARY: Uveal melanoma is a cancer that develops from melanocytes in the eye. This disease is extremely rare and has a strong predilection for liver metastasis, which has a poor long-term prognosis with overall survival of 6 months and 1 year mortality of 80%. Immunotherapy and checkpoint inhibitors have revolutionized treatment for cutaneous melanoma but have largely been proven to be ineffective in uveal melanoma. The poor response associated with systemic chemotherapy and immunotherapy approaches coupled with the fact that most metastatic disease is isolated to the liver suggests a persistent need for regional treatment approaches. Of regional therapies, hepatic perfusion continued to be associated with the best survival outcomes of up to 27 months. Additional therapies that target the unique biology of uveal melanoma are desperately needed. Until these treatments are developed and proven, isolated hepatic perfusion remains a viable treatment option. ABSTRACT: Uveal melanoma is a cancer that develops from melanocytes in the posterior uveal tract. Metastatic uveal melanoma is an extremely rare disease that has a poor long-term prognosis, limited treatment options and a strong predilection for liver metastasis. Median overall survival has been reported to be 6 months and 1 year mortality of 80%. Traditional chemotherapy used in cutaneous melanoma is ineffective in uveal cases. Surgical resection and ablation is the preferred therapy for liver metastasis but is often not feasible due to extent of disease. In this review, we will explore treatment options for liver metastases from uveal melanoma, with a focus on isolated hepatic perfusion (IHP). IHP offers an aggressive regional therapy approach that can be used in bulky unresectable disease and allows high-dose chemotherapy with melphalan to be delivered directly to the liver without systemic effects. Long-term median overall survival has been reported to be as high as 27 months. We will also highlight the poor responses associated with checkpoint inhibitors, including an overview of the biological rationale driving this lack of immunotherapy effect for this disease. The persistent failure of traditional treatments and immunotherapy suggest an ongoing need for regional surgical approaches such as IHP in this disease.