Immunotherapy effective for rare melanoma, study finds

Dr. Antoni Ribas, senior author of the study and director of the UCLA Health Jonsson Comprehensive Cancer Center’s Tumour Immunology Program, is in his laboratory. Photo courtesy UCLA Health

A clinical trial led by researchers at the University of California, Los Angeles (UCLA) has found that pembrolizumab, a widely used immunotherapy, can dramatically extend the lives of patients with unresectable advanced desmoplastic melanoma—a rare, aggressive skin cancer long resistant to standard treatments.

The phase 2 SWOG S1512 trial, published in Nature Medicine, evaluated the anti–programmed death protein 1 (PD-1) checkpoint inhibitor as a single agent for patients with metastatic desmoplastic melanoma deemed inoperable.

“Patients with advanced desmoplastic melanoma demonstrate a high response rate to single-agent PD-1 blockade therapy, reinforcing the use of anti-PD-1 as the preferred treatment option for this disease,” said Dr. Antoni Ribas in a press release. “It offers a less invasive, more targeted approach compared to surgery, radiation, or combination immunotherapies, which can have more severe side effects.” Dr. Ribas is the study’s senior author and director of the UCLA Health Jonsson Comprehensive Cancer Center’s Tumor Immunology Program.

Pembrolizumab was administered intravenously every three weeks for up to two years to 27 patients whose disease had spread. The results showed 37% achieved complete response, with all signs of cancer disappearing, and an overall 89% objective response rate, encompassing both complete and significant tumour reductions. These responses were typically swift—many patients exhibited tumour shrinkage within just two months of starting treatment. After three years, 84% of subjects were alive and 72% had no evidence of cancer progression.

“Desmoplastic melanoma is a distinct subtype of melanoma known to have preexisting immune infiltrates and high ultraviolet light damage, resulting in a high tumour mutational burden. We hypothesized that this may result in high response rates with single-agent anti-programmed death protein 1 (PD-1) therapy,” the study authors noted. The marked immune signatures and mutational landscape of desmoplastic melanoma may make these tumours especially visible to the immune system—helping to explain the robust response.

While immunotherapy was generally well-tolerated, the study population, comprising predominantly older adults with comorbidities, experienced a higher frequency of adverse events. Ten patients (37%) had grade 3 or 4 toxicities, and nine (33%) discontinued treatment due to side effects. Notably, discontinuation did not diminish overall outcomes, with remissions often sustained after therapy cessation.

“The promising results from this trial show that pembrolizumab can offer durable benefit for patients with a melanoma subtype that previously had no successful treatment options, and now we know that desmoplastic melanoma is among the cancers with the highest response rates to the anti-PD-1 class of cancer immunotherapies,” said Dr. Ribas.