Treatments, Patient Characteristics Affect Uveal Melanoma Survival

Patients with metastatic uveal melanoma (UM) experienced improved survival outcomes if treated with immune checkpoint inhibitors (ICIs, a type of immunotherapy that assists the immune system find and fight cancer), including anti-CTLA-4 and anti-PD-1 therapies, according to the findings of a new study.

Factors such as female sex, extrahepatic-only metastases (secondary malignant growths not in the liver), better baseline performance status on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale, laboratory measurements and metastasis location all “contributed to a more than 2-fold reduction in death risk,” according to the authors of the study, published in the journal Cancer.

Uveal melanoma, the authors of the study noted, is the most common intraocular (within the eyeball) cancer among adult patients.

“Although treatment modalities for the primary tumor have excellent local control (>95%), roughly 27% to 34% of patients develop distant metastases within 10 years,” the authors wrote. “Once clinical metastases are detected, median overall survival is usually less than 1 year.”

“Uveal melanoma, sometimes called ocular melanoma or eye melanoma, is the most common eye tumor in adults, but it is a very rare subtype of melanoma, only affecting about six per million people,” Dr. Marlana Orloff, an associate professor of medicine at Thomas Jefferson University Hospital in Philadelphia, explained during CURE®’s Educated Patient Sound Bites on metastatic uveal melanoma in June.

“We don’t know what causes eye melanoma,” Orloff said. “Unlike skin melanoma, we don’t think UV (ultraviolet radiation) is the cause. However, risk factors are similar to eye melanoma in being fair skinned and having light eyes. For most patients with eye melanoma, it is a spontaneous disorder, meaning it isn’t necessarily inherited. But in about 1% to 2% of all eye melanoma, they can inherit a genetic mutation called BAP1 syndrome.”

The study was a retrospective review of 89 patients with metastatic UM, 71 at Yale New Haven Health in the initial cohort and 18 in the validation cohort at Memorial Sloan Kettering Cancer Center in New York.

The cohort of Yale patients were treated between March 2007 and November 2021, with a median follow-up of 19.8 months and a median overall survival (OS, the time following treatment that a patient is still alive) of 21.8 months. Development of hepatic metastases and a low ECOG score were both associated with worse survival outcomes. Patients in the validation cohort were treated via the ocular oncology service at Memorial Sloan Kettering between February 2005 and June 2022.

The Food and Drug Administration (FDA) approved Kimmtrak (tebentafusp-tebn) for the treatment of patients with unresectable or metastatic uveal melanoma who are HLA-A*02:01 positive.

“Kimmtrak is a newer type of immunotherapy, also called a T-cell redirector, that acts like a magnet that combines your own immune system, your T cell, and drags it over to a target on the cancer, something called gp100 (glycoprotein 100), and kind of forces them to engage, hopefully allowing the immune system to kill the cancer,” Orloff explained to CURE®.

But, as the authors of the recent Cancer study explained, only about half of the population is HLA-A*02:01-positive.

“Therefore, there is still a critical need to identify alternative treatment options for patients who may not be eligible to receive (Kimmtrak),” the authors wrote.

Kimmtrak is first immune therapy agent to show significant overall survival impact in a randomized trial setting, with a median OS of 21.7 months versus a median OS of 16 months in a phase 3 trial, the Cancer authors wrote, nothing that “this has renewed interest in immune therapy as a therapeutic option for metastatic uveal melanoma.”

Participants in the Cancer study who received treatment with any ICI had a median OS of 29.2 months.

“Nevertheless, our data, along with those from the subgroup analysis in the (Kimmtrak) study, suggest that a large randomized controlled trial comparing anti–CTLA‐4 therapy to (Kimmtrak), ideally to patients with the HLA‐A*02:01 haplotype, may be warranted,” they wrote.

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