High Response of Desmoplastic Melanomas to PD-1 Blockade
WEDNESDAY, Jan. 17, 2018 -- Patients with desmoplastic melanoma have a high level of objective tumor response to treatment with antibodies to block programmed cell death 1 (PD-1) or PD-1 ligand (PD-L1), according to a study published online Jan. 10 in Nature.
Zeynep Eroglu, M.D., from the University of California, Los Angeles, and colleagues conducted an analysis of 60 patients with advanced desmoplastic melanoma who had received treatment with antibodies to block PD-1 or PD-L1.
The researchers found that 70 percent of the patients had objective tumor responses, including 32 percent with a complete response. A high mutational load and frequent NF1 mutations were seen in these tumors, based on whole-exome sequencing. The percentage of PD-L1-positive cells was higher in the tumor parenchyma in desmoplastic melanomas than in non-desmoplastic melanomas (P = 0.04); there was a strong correlation for these cells with increased CD8 density and PD-L1 expression in the tumor invasive margin.
"Patients with advanced desmoplastic melanoma derive substantial clinical benefit from PD-1 or PD-L1 immune checkpoint blockade therapy, even though desmoplastic melanoma is defined by its dense desmoplastic fibrous stroma," the authors write. "The benefit is likely to result from the high mutational burden and a frequent pre-existing adaptive immune response limited by PD-L1 expression."
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Posted: January 2018