Patients with the rare melanoma subtype known as desmoplastic melanoma are more responsive to immune-activating anti-PD-1/PD-L1 therapies than previously assumed, researchers report in a paper published online ahead of print in Nature (Jan. 10, 2018).
“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,” said lead author Dr. Zeynep Eroglu, in a press release from the Moffitt Cancer Center in Tampa, Fla.
Dr. Eroglu is a medical oncologist in the Department of Cutaneous Oncology at Moffitt Cancer Center and an assistant professor in the Department of Oncologic Sciences at the University of South Florida Morsani College of Medicine in Tampa.
The authors analyzed 60 patients who had advanced desmoplastic melanoma and who had been treated with antibodies to block programmed cell death 1 (PD-1) or PD-1 ligand (PD-L1).
Among the 60 patients, objective tumour responses were observed in 42 patients (70%; 95% confidence interval 57–81%). Eighteen of the patients (32%) had a complete response with the tumours entirely disappearing.
Long-term survival was also good, with 74% of patients still alive more than two years after beginning treatment.
A 70% response rate is one of the highest reported for anti-PD-1/PD-L1 therapies, the authors note, and is higher than response rates commonly observed in patients with other subtypes of melanoma—usually approximately 35 to 40%.
Working to find out why these cancers were responding to anti-PD-1/PDL1 therapies, the authors determined that desmoplastic melanomas had high levels of DNA mutations, with NF-1 mutations being the most common driving genetic event. They also demonstrated that desmoplastic melanomas have the pre-existing immune cells and proteins necessary to mount an immune response against cancer cells. A comparison of tissue biopsies from patients with desmoplastic melanoma and non-desmoplastic melanoma revealed that the desmoplastic melanomas had more cells with high levels of the PD-L1 protein in both the tumours and the invading edges of the tumour.
The desmoplastic melanomas studied also had high levels of CD8 T cells, which are important for the efficacy of immune-activating drugs.
“Often, combinations of two immunotherapy drugs are used to treat patients with melanoma to try to improve tumour response rates and survival above current reported rates,” said Dr. Eroglu. “However, these combinations can lead to significantly higher rate of severe side-effects than treatment with anti-PD-1 therapy alone. 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.”