A rare type of malignant melanoma is treatable with immunotherapies, according to a new study — overturning previous beliefs that the cancer, called desmoplastic melanoma, is not treatable with such medications.
The specific treatments used prevent the interaction between the molecule PD-L1 and its receptor, PD-1. When PD-L1 binds to PD-1, the body dampens its immune response. When this signal is blocked, the immune system can activate and attack cancer cells.
Until now, researchers assumed that the density of desmoplastic melanoma tumors would prevent activated immune cells from reaching their targets.
But the study, “High response rate to PD-1 blockade in desmoplastic melanomas,” published in the journal Nature, found that an immunotherapy had a high success rate in patients with this melanoma. The results point to a viable therapy for a cancer that rarely responds to chemotherapy or other, targeted treatments.
“Our findings challenge the previous school of thought that immunotherapy would offer little benefit to patients with desmoplastic melanoma due to the dense tissue architecture of these tumors,” Dr. Zeynep Eroglu, study author from the Moffitt Cancer Center in Florida, said in a press release.
“These tumors, in fact, have the necessary biological ingredients to be very effective targets for anti-PD-1 drugs,” she added.
Moffitt scientists worked with colleagues at the University of California, Los Angeles to conduct a review of the cases of 60 desmoplastic melanoma patients who had been treated with such medications.
Patients included in the study were mainly treated with Keytruda (pembrolizumab) — developed by Merck — or Bristol-Myers Squibb’s Opdivo (nivolumab). Both block PD-1. Three patients had received the treatments in combination with the CTLA-4 inhibitor Yervoy (ipilimumab), another immunotherapy. Some were also treated with an experimental PD-L1 blocker.
To the team’s surprise, 42 of these patients, or 70%, responded to the treatment — a particularly high level of response for these drugs. Patients with other melanoma types, for example, have response rates of about 35 to 40%.
Among the patients who responded, 32% had a complete eradication of their tumor.
The team analyzed the tumor tissue to explain their result: They found that the tumors, as well as their invasive margins, contained high levels of PD-L1. High levels of PD-L1 in tissue is often linked to a good response to PD-1 blockers.
The tumors also had high levels of the immune cells needed to attack the cancer cells.
“Often, combinations of two immunotherapy drugs are used to treat patients with melanoma to try to improve tumor response rates and survival above current reported rates,” said Eroglu. However, she continued, the combinations also risk producing severe side-effects.
“Our data suggest 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.”
