Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
Drug Resistance, Neoplasm
/ genetics
Female
Genotype
Humans
Immune Checkpoint Inhibitors
/ therapeutic use
Male
Melanoma
/ drug therapy
Middle Aged
Polymorphism, Single Nucleotide
Programmed Cell Death 1 Receptor
/ genetics
Progression-Free Survival
Retrospective Studies
PD1
immunotherapy
metastatic melanoma
polymorphism
predictive biomarker
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
25
02
2021
accepted:
21
05
2021
entrez:
28
6
2021
pubmed:
29
6
2021
medline:
21
10
2021
Statut:
epublish
Résumé
A significant number of patients (pts) with metastatic melanoma do not respond to anti-programmed cell death 1 (PD1) therapies. Identifying predictive biomarkers therefore remains an urgent need. We retrospectively analyzed plasma DNA of pts with advanced melanoma treated with PD-1 antibodies, nivolumab or pembrolizumab, for five PD-1 genotype single nucleotide polymorphisms (SNPs): PD1.1 (rs36084323, G>A), PD1.3 (rs11568821, G>A), PD1.5 (rs2227981, C>T) PD1.6 (rs10204225, G>A) and PD1.9 (rs2227982, C>T). Clinico-pathological and treatment parameters were collected, and presence of SNPs correlated with response, progression free survival (PFS) and overall survival (OS). 115 patients were identified with a median follow up of 18.7 months (range 0.26 - 52.0 months). All were Caucasian; 27% BRAF V600 mutation positive. At PD-1 antibody commencement, 36% were treatment-naïve and 52% had prior ipilimumab. The overall response rate was 43%, 19% achieving a complete response. Overall median PFS was 11.0 months (95% CI 5.4 - 17.3) and median OS was 31.1 months (95% CI 23.2 - NA). Patients with the G/G genotype had more complete responses than with A/G genotype (16.5%
Identifiants
pubmed: 34177913
doi: 10.3389/fimmu.2021.672521
pmc: PMC8220213
doi:
Substances chimiques
Biomarkers, Tumor
0
Immune Checkpoint Inhibitors
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
672521Informations de copyright
Copyright © 2021 Parakh, Musafer, Paessler, Witkowski, Suen, Tutuka, Carlino, Menzies, Scolyer, Cebon, Dobrovic, Long, Klein and Behren.
Déclaration de conflit d'intérêts
MC has a consultant advisory role with BMS, MSD, Amgen, Novartis, Pierre Fabre, Roche, Sanofi, Merck and Co, Ideaya, Regeneron, Nektar, Eisai and Q biotics and OncoSec. AMM is a consultant advisor to BMS, MSD, Novartis, Roche, Pierre-Fabre, QBiotics. RAS has received fees for professional services from Qbiotics, Novartis, Merck Sharp & Dohme, NeraCare, AMGEN Inc., Bristol-Myers Squibb, Myriad Genetics, and GlaxoSmithKline. JC has sat on advisory boards for Novartis and GSK. GL is consultant advisor for Aduro Biotech Inc, Amgen Inc, Array Biopharma inc, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Hexel AG, Highlight Therapeutics S.L., Merck Sharpe & Dohme, Novartis Pharma AG, OncoSec, Pierre Fabre, QBiotics Group Limited, Regeneron Pharmaceuticals Inc, SkylineDX B.V., and Specialised Therapeutics Australia Pty Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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