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High Response Rate to Anti PD-1 Therapy in Desmoplastic Melanoma

ABSTRACT:

Desmoplastic melanoma (DM) is a rare subtype of melanoma characterized by dense fibrous stroma, resistance to chemotherapy and a lack of actionable driver mutations, but is highly associated with ultraviolet light DNA damage. We analysed 60 patients with advanced DM treated with programmed cell death 1 (PD-1) or PD-1 ligand (PD-L1) blocking antibody therapy. Objective tumor responses were observed in 42 of the 60 patients (70%, 95% confidence interval 57-81%), including 19 patients (32% overall) with a complete response. Whole-exome sequencing revealed a high mutational load and frequent NF-1 mutations (14 out of 17 cases). Immunohistochemistry (IHC) analysis from 19 DM and 13 non-DM revealed a higher percentage of PD-L1 positive cells in the tumor parenchyma in DM (p = 0.04), highly associated with increased CD8 density and PD-L1 expression in the tumor invasive margin. Therefore, patients with advanced DM derive significant clinical benefit from PD-1/PD-L1 immune checkpoint blockade therapy despite being a cancer defined by its dense desmoplastic fibrous stroma. The benefit is likely derived from the high mutational burden and a frequent pre-existing adaptive immune response limited by PD-L1 expression.

PROVIDER: phs001469 | dbGaP |

SECONDARY ACCESSION(S): PRJNA414014PRJNA414013

REPOSITORIES: dbGaP

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			Action	DRS
	GapExchange_phs001469.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	Study_Report.phs001469.Anti_PD1_Therapy.v1.p1.MULTI.pdf	Pdf
	manifest_phs001469.Anti_PD1_Therapy.v1.p1.c1.HMB-PUB-NPU-MDS.pdf	Pdf
	datadict_v2.xsl	Other

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