The Future of Checkpoint Inhibitors in Uveal Melanoma: A Narrative Review

Ophthalmol Ther. 2024 May;13(5):1103-1123. doi: 10.1007/s40123-024-00913-2. Epub 2024 Mar 18.

Abstract

Introduction: Immune checkpoint inhibitors have made tremendous progress over the last decade in the treatment of cutaneous melanoma, but their application in uveal melanoma treatment is less successful, owing in part to the immunological privilege of the eye and the liver, the most frequent site of metastasis. Nevertheless, the therapeutic outcomes reported currently are less pessimistic.

Methods: In this review, we provide an overview of recent studies of immune checkpoint inhibitors in uveal melanoma and its metastasis and classify studies in this field into three groups: monotherapy of immune checkpoint inhibitors, dual-agent immune checkpoint inhibitors, and immune checkpoint inhibitors combined with other systemic or regional therapies.

Results: Briefly, monotherapy with immune checkpoint inhibitors performed poorly. Dual-agent immune checkpoint inhibitors had slightly better outcomes than traditional treatments, especially in specific patient populations. As for the combination therapy, the combination with other systemic therapies did not show superiority over dual-agent immune checkpoint inhibitors, but combination with hepatic regional therapies was quite promising. Moreover, research on emerging checkpoints is currently limited to the stage of mechanistic studies.

Conclusion: We propose that immune checkpoint inhibitors remain alternative treatments for patients with uveal melanoma, but factors such as cost-effectiveness should also be taken into account. The combination therapy with immune checkpoint inhibitors deserves to be further explored.

Keywords: Anti-CTLA 4; Anti-PD 1/L1; Immune checkpoint inhibitors; Immunotherapy; Liver metastasis; Uveal melanoma.

Publication types

  • Review