Tumor mutational load predicts survival after immunotherapy across multiple cancer types Journal Article


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.
Article 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:
Notes: Letter -- Export Date: 1 March 2019 -- Source: Scopus
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MSK Authors
  1. Timothy Chan
    292 Chan
  2. Paul Russo
    530 Russo
  3. Dean Bajorin
    567 Bajorin
  4. Robert Motzer
    1012 Motzer
  5. Leonard B Saltz
    703 Saltz
  6. Ronald P DeMatteo
    634 DeMatteo
  7. Jedd D Wolchok
    806 Wolchok
  8. David Solit
    622 Solit
  9. Neil Howard Segal
    156 Segal
  10. Viviane S Tabar
    160 Tabar
  11. Ronglai Shen
    156 Shen
  12. Philip H Gutin
    162 Gutin
  13. Cameron Brennan
    183 Brennan
  14. Nadeem Riaz
    308 Riaz
  15. Geoffrey Yuyat Ku
    148 Ku
  16. Antonio Marcilio Padula Omuro
    196 Omuro
  17. Nancy Y. Lee
    685 Lee
  18. Naiyer A Rizvi
    166 Rizvi
  19. Zsofia Kinga Stadler
    249 Stadler
  20. Thomas Kaley
    121 Kaley
  21. Yelena Yuriy Janjigian
    231 Janjigian
  22. Marc Ladanyi
    1129 Ladanyi
  23. Martin Henner Voss
    202 Voss
  24. Jamie Erin Chaft
    193 Chaft
  25. David G Pfister
    317 Pfister
  26. Gopakumar Vasudeva Iyer
    209 Iyer
  27. Shrujal S Baxi
    96 Baxi
  28. Richard J Wong
    284 Wong
  29. Gregory J Riely
    462 Riely
  30. Mrinal M Gounder
    139 Gounder
  31. Rona Denit Yaeger
    158 Yaeger
  32. Sandra Pierina D'Angelo
    161 D'Angelo
  33. Christopher Barker
    161 Barker
  34. Luc Morris
    182 Morris
  35. Charlotte Eielson Ariyan
    113 Ariyan
  36. Bernard Bochner
    389 Bochner
  37. Ahmet Zehir
    272 Zehir
  38. Alan Loh Ho
    145 Ho
  39. Michael Forman Berger
    564 Berger
  40. Howard Scher
    1036 Scher
  41. William Douglas Tap
    216 Tap
  42. Matthew David Hellmann
    327 Hellmann
  43. Jonathan Eric Rosenberg
    369 Rosenberg
  44. Abraham Ari Hakimi
    232 Hakimi
  45. Jose T Baselga
    480 Baselga
  46. Charles Rudin
    299 Rudin
  47. Pedram Razavi
    102 Razavi
  48. Chung-Han   Lee
    86 Lee
  49. David   Barron
    11 Barron
  50. Emmet John Jordan
    46 Jordan
  51. Manuela F Berger
    6 Berger