Uveal melanoma

Uveal melanoma is rare and constitutes 5% of all melanomas. They develop mainly from pigment cells of the choroidea, less commonly from the ciliary body or the iris of the eye. The treatment of primary uveal melanoma includes surgery and radiation therapy. Especially large tumors and those with extraocular extension are enucleated. Smaller tumors can be irradiated with plaque brachytherapy or protons. Follow-up, which consists of ophthalmologic examinations, liver ultrasound, and may include assessment of the transaminases in the peripheral blood, is ideally based on the risk profile of the primary tumor and performed every 3-6 months. According to the genetic risk profile, 50% of patients develop distant metastasis, mainly in the liver. Therefore, in addition to systemic therapy, local liver-directed therapies such as chemoperfusion/chemosaturation, transarterial chemoembolization (TACE), and selective internal radiotherapy (SIRT) can be administered. To date, however, there is no definitive evidence that these treatments not only inhibit progression in the liver but improve overall survival. Treatment of choice in patients with metastases is the newly approved immunotherapy with tebentafusp, a bispecific protein consisting of a gp100-TCR (T cell receptor) fused to a CD3 antibody leading to activation of T cells in the microenvironment of the uveal melanoma. It is the first drug proven to lead to a significant survival benefit for patients with metastasized uveal melanoma compared with other systemic therapies such as immune checkpoint inhibitors and chemotherapy. Interestingly, patients with progressing metastases also have a survival benefit. However, treatment can only be given to patients with the human leukocyte antigen (HLA)-A0201 phenotype to which the TCR was designed and which is present in approximately 50% of patients. Further promising new drugs are under development.