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    Promising advances in uveal melanoma treatment

    Light-activated nanoparticles, immune therapy may be change clinical paradigm

    Immunotherapy and other investigational treatments appear to be promising for uveal melanoma, according to Carol Shields, MD.

    “There have been interesting new avenues for therapy,” said Dr. Shields, co-director, Ocular Oncology Service, Wills Eye Hospital, Philadelphia.

    Among the new treatments are light-activated AU-011, targeted drugs, checkpoint inhibitors, vaccines, and anti-VEGF therapy.

    Uveal melanoma is particularly deadly because after starting in the back of the eye, it grows into choroidal vessels. From there, it travels elsewhere in the body and is particularly likely to spread to the liver and lungs.

    “Once it grows there, you’ve got a real bad problem,” Dr. Shields said.

    Until now, the main treatments have been plaque or proton-beam radiation therapy, she said. Occasionally, an entire eye must be removed. Chemotherapy has been used in the past to treat systemic metastases, but this is associated with bad side effects.

    Specialists are excited to see such alternatives as immunotherapy on the horizon, Dr. Shields said.

    “Immune therapy is a great alternative for melanoma. It’s a cool way to educate the patient’s body to fight back with immune vigor rather than poisoning it with chemotherapy,” she said.

    The approach has had success in leukemia, lung cancer, and skin cancer.

    One class of immunotherapy, checkpoint inhibitors, has generated some excitement because of its success in skin melanoma. However, these drugs have fallen short in hopes for uveal melanoma, said Dr. Shields.

    Checkpoint inhibitors block mechanisms that keep T cells in check. Ipilimumab targets CTLA-4 receptors while pembrolizumab and nivolumab target PD-1 receptors.

    “They allow the T cells to go bananas and fight everything in the body,” she said.

    These medications have cut the fatality rate for metastatic skin melanoma from about 100% to about 90%, with former President Jimmy Carter perhaps the most famous case of a patient who was saved.

    “The bad news is that there are many, many side-effects, and some patients can’t tolerate these medications because they cause a strong autoimmune response,” Dr. Shields said.

    Even more disappointing for ophthalmologists, the response rate in uveal melanoma studies so far has been about 3%. That contrasts with about 50% in skin melanoma.

    “Still, just the fact that the immune system can cure skin melanoma really excites us,” she said, “so we’re hoping we can hit on some medication that might be effective for uveal melanoma patients.”

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