Advances and new trends in the clinical management of malignant uveal melanoma patients

Malignant uveal melanoma is a rare eye cancer that metastasizes in approximately 50% of patients. Despite the relatively successful treatment of the primary tumors and availability of reliable prognostic markers, there are still few treatment options for metastatic uveal melanoma. Chemotherapy, immune checkpoint inhibitors, and targeted therapies have not achieved satisfactory results so far. In recent years, several studies have been published demonstrating the significant role of epigenome deregulation in disease progression, and diverse groups of epigenetic inhibitors are undergoing clinical testing. Recently, significant progress has been made by utilizing omics technologies and singlecell approaches to gain a better understanding of the uveal melanoma tumor microenvironment. Furthermore, ongoing research is focused on multiple emerging regional and systematic therapeutic strategies aimed at addressing liver metastases. Tebentafusp is a specific fusion protein consisting of a T-cell receptor conjugated to an antibody fragment targeting CD3. Its TCR targeting domain binds with high affinity to the gp100 peptide presented by uveal melanoma tumor cells. Tebentafusp is the first effective therapy approved by regulatory agencies in January 2022 (FDA) and April 2022 (EMA) for treating human leukocyte antigen (HLA)-A*02:01 positive metastatic uveal melanoma patients. Its successful development emphasizes that, even in uveal melanoma, which was considered unresponsive to immunotherapy, high treatment efficiency can be achieved through the appropriate modulation of the antitumor immune response. (author)