Synapse - Tumor mutational load predicts survival after immunotherapy across multiple cancer types

Tumor mutational load predicts survival after immunotherapy across multiple cancer types Research Letter

Authors:	Samstein, R. M.; Lee, C. H.; Shoushtari, A. N.; Hellmann, M. D.; Shen, R.; Janjigian, Y. Y.; Barron, D. A.; Zehir, A.; Jordan, E. J.; Omuro, A.; Kaley, T. J.; Kendall, S. M.; Motzer, R. J.; Hakimi, A. A.; Voss, M. H.; Russo, P.; Rosenberg, J.; Iyer, G.; Bochner, B. H.; Bajorin, D. F.; Al-Ahmadie, H. A.; Chaft, J. E.; Rudin, C. M.; Riely, G. J.; Baxi, S.; Ho, A. L.; Wong, R. J.; Pfister, D. G.; Wolchok, J. D.; Barker, C. A.; Gutin, P. H.; Brennan, C. W.; Tabar, V.; Mellinghoff, I. K.; DeAngelis, L. M.; Ariyan, C. E.; Lee, N.; Tap, W. D.; Gounder, M. M.; D’Angelo, S. P.; Saltz, L.; Stadler, Z. K.; Scher, H. I.; Baselga, J.; Razavi, P.; Klebanoff, C. A.; Yaeger, R.; Segal, N. H.; Ku, G. Y.; DeMatteo, R. P.; Ladanyi, M.; Rizvi, N. A.; Berger, M. F.; Riaz, N.; Solit, D. B.; Chan, T. A.; Morris, L. G. T.
Title:	Tumor mutational load predicts survival after immunotherapy across multiple cancer types
Abstract:	Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in selected cancer types suggest that tumor mutational burden (TMB) may predict clinical response to ICI. To examine this association more broadly, we analyzed the clinical and genomic data of 1,662 advanced cancer patients treated with ICI, and 5,371 non-ICI-treated patients, whose tumors underwent targeted next-generation sequencing (MSK-IMPACT). Among all patients, higher somatic TMB (highest 20% in each histology) was associated with better overall survival. For most cancer histologies, an association between higher TMB and improved survival was observed. The TMB cutpoints associated with improved survival varied markedly between cancer types. These data indicate that TMB is associated with improved survival in patients receiving ICI across a wide variety of cancer types, but that there may not be one universal definition of high TMB. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
Journal Title:	Nature Genetics
Volume:	51
Issue:	2
ISSN:	1061-4036
Publisher:	Nature Publishing Group
Date Published:	2019-02-01
Start Page:	202
End Page:	206
Language:	English
DOI:	10.1038/s41588-018-0312-8
PUBMED:	30643254
PROVIDER:	scopus
PMCID:	PMC6365097
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85059965982&doi=10.1038%2fs41588-018-0312-8&partnerID=40&md5=f56c4ad03646a21866a9d67b204eec72
Notes:	Letter -- Export Date: 1 March 2019 -- Source: Scopus