Moffitt Cancer Center (FL, USA) researchers have discovered that desmoplastic melanoma patients are more responsive to anti-PD-1/PD-L1 therapies than previously assumed; the findings were published recently in Nature.
Desmoplastic melanoma is characterized by a dense fibrous stroma, resistance to chemotherapy and a lack of actionable driver mutations. It was previously believed that the tissue architecture of desmoplastic melanomas would reduce the ability of immune cells to infiltrate the tumor area and limit the effectiveness of immune-activating drugs.
In this study, researchers analyzed 60 patients with advanced desmoplastic melanoma who had previously been treated with antibodies to block PD-1/PD-L1. They discovered that 70% of patients had a significant response to treatment and that nineteen (32%) of these patients had a complete response. Furthermore, 74% of patients were still alive more than 2 years after beginning treatment.
Moffitt researchers went onto collaborate with 10 US and international cancer centers, to determine the biological reasons why patients with desmoplastic melanoma may benefit from drugs that target PD-1 or PD-L1.
Whole-exome sequencing revealed a high mutational load and frequent NF1 mutations (fourteen out of seventeen cases) in these tumors. The researchers also compared tissue biopsies from patients with desmoplastic melanoma and non-desmoplastic melanoma and revealed a higher percentage of PD-L1-positive cells within both the tumor and the invading edges of the tumor.
“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,” first author Zeynep Eroglu from Moffitt Cancer Center, explained.
“These tumors in fact have the necessary biological ingredients to be very effective targets for anti-PD-1 drugs,” she continued. “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. 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,” she concluded.