Authors
Douglas B Johnson, Garrett M Frampton, Matthew J Rioth, Erik Yusko, Yaomin Xu, Xingyi Guo, Riley C Ennis, David Fabrizio, Zachary R Chalmers, Joel Greenbowe, Siraj M Ali, Sohail Balasubramanian, James X Sun, Yuting He, Dennie T Frederick, Igor Puzanov, Justin M Balko, Justin M Cates, Jeffrey S Ross, Catherine Sanders, Harlan Robins, Yu Shyr, Vincent A Miller, Philip J Stephens, Ryan J Sullivan, Jeffrey A Sosman, Christine M Lovly
Publication date
2016/11/1
Journal
Cancer immunology research
Volume
4
Issue
11
Pages
959-967
Publisher
American Association for Cancer Research
Description
Therapeutic antibodies blocking programmed death-1 and its ligand (PD-1/PD-L1) induce durable responses in a substantial fraction of melanoma patients. We sought to determine whether the number and/or type of mutations identified using a next-generation sequencing (NGS) panel available in the clinic was correlated with response to anti–PD-1 in melanoma. Using archival melanoma samples from anti–PD-1/PD-L1-treated patients, we performed hybrid capture–based NGS on 236–315 genes and T-cell receptor (TCR) sequencing on initial and validation cohorts from two centers. Patients who responded to anti–PD-1/PD-L1 had higher mutational loads in an initial cohort (median, 45.6 vs. 3.9 mutations/MB; P = 0.003) and a validation cohort (37.1 vs. 12.8 mutations/MB; P = 0.002) compared with nonresponders. Response rate, progression-free survival, and overall survival were superior in the high …
Total citations
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