Dense Tissue Is Not an Obstacle to Immunotherapy in Desmoplastic Melanoma

Researchers have recently discovered that immunotherapy agents including anti-PD-1/PD-L1 inhibitors have potential to effectively treat desmoplastic melanoma, even though the dense tissue associated with this rare skin cancer would seem to preclude it. Desmoplastic melanoma accounts for about 4 percent of all melanoma cases.

A small but powerful study by a team of scientists from 10 different cancer centers around the globe — including Moffitt Cancer Center and UCLA – assessed 60 adults with advanced desmoplastic melanoma who received either pembrolizumab (Keytruda) or nivolumab (Opdivo). Forty-two patients (about 70%) had a significant response, where their tumor shrunk in size, and 19 of these patients had a complete response. None of them faced recurrence to date.

“Our finding challenges the previous school of thought that immunotherapy would offer little benefit for patients with desmoplastic melanoma due to the dense tissue architecture of these tumors. These tumors in fact have the necessary biological ingredients to be very effective targets for anti-PD-1 drugs,” Zeynep Eroglu, MD, assistant member of the Cutaneous Oncology Department at Moffitt said in a release.

After profiling desmoplastic melanoma tumors, the researchers discovered that the majority — 14 out of 17 patients – had high mutational activity. Further, when compared to other melanoma types, desmoplastic disease actually had a higher percentage of PD-L1 expression.

Down the road, these findings can have an impact on the way that desmoplastic melanoma is treated, potentially improving what is currently a poor prognosis for many patients. This is an unmet need, with the disease often being resistant to chemotherapy, and it is traditionally thought of as having a lack of targetable mutations.

The studies have paved the way for a new clinical trial to open, which will span 100 sites across the United States. The study will test the outcomes of pre-surgical pembrolizumab for patients with desmoplastic melanoma.

If a single-agent immunotherapy regimen, like one using pembrolizumab or nivolumab, is approved for this patient population, not only will that offer a new option, but it could also give patients the opportunity to dodge some unpleasant side effects.

“Often, combinations of two immunotherapy drugs are used to treat patients with melanoma to try to improve tumor response rates and survival about current reported rates. However, these combinations can lead to significantly higher rate of severe side effects than treatment with anti-PD-1 therapy alone,” Eroglu said. “Our data suggests that single-agent anti-PD-1 therapy may well be sufficient for patients with desmoplastic melanoma, potentially sparing them the increased toxicities generally observed with combinations of immunotherapies.”