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Tumor mutational load predicts survival after immunotherapy across multiple cancer types

2019; Nature Portfolio; Volume: 51; Issue: 2 Linguagem: Inglês

10.1038/s41588-018-0312-8

1546-1718

Robert M. Samstein, Chung‐Han Lee, Alexander N. Shoushtari, Matthew D. Hellmann, Ronglai Shen, Yelena Y. Janjigian, David Barron, Ahmet Zehir, Emmet Jordan, Antonio Omuro, Thomas Kaley, Sviatoslav M. Kendall, Robert J. Motzer, A. Ari Hakimi, Martin H. Voss, Paul Russo, Jonathan E. Rosenberg, Gopa Iyer, Bernard H. Bochner, Dean F. Bajorin, Hikmat Al‐Ahmadie, Jamie E. Chaft, Charles M. Rudin, Gregory J. Riely, Shrujal S. Baxi, Alan L. Ho, Richard J. Wong, David G. Pfister, Jedd D. Wolchok, Christopher A. Barker, Philip H. Gutin, Cameron Brennan, Viviane Tabar, Ingo K. Mellinghoff, Lisa M. DeAngelis, Charlotte E. Ariyan, Nancy Y. Lee, William D. Tap, Mrinal M. Gounder, Sandra P. D’Angelo, Leonard B. Saltz, Zsofia K. Stadler, Howard I. Scher, José Baselga, Pedram Razavi, Christopher A. Klebanoff, Rona Yaeger, Neil H. Segal, Geoffrey Y. Ku, Ronald P. DeMatteo, Marc Ladanyi, Naiyer A. Rizvi, Michael F. Berger, Nadeem Riaz, David B. Solit, Timothy A. Chan, Luc G.T. Morris,

Lung Cancer Treatments and Mutations

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.