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
    258 Chan
  2. Paul Russo
    495 Russo
  3. Dean Bajorin
    505 Bajorin
  4. Robert Motzer
    909 Motzer
  5. Leonard B Saltz
    665 Saltz
  6. Ronald P DeMatteo
    627 DeMatteo
  7. Jedd D Wolchok
    754 Wolchok
  8. David Solit
    541 Solit
  9. Neil Howard Segal
    139 Segal
  10. Viviane S Tabar
    137 Tabar
  11. Ronglai Shen
    143 Shen
  12. Philip H Gutin
    161 Gutin
  13. Cameron Brennan
    165 Brennan
  14. Nadeem Riaz
    258 Riaz
  15. Geoffrey Yuyat Ku
    119 Ku
  16. Antonio Marcilio Padula Omuro
    193 Omuro
  17. Nancy Y. Lee
    616 Lee
  18. Naiyer A Rizvi
    165 Rizvi
  19. Zsofia Kinga Stadler
    199 Stadler
  20. Thomas Kaley
    107 Kaley
  21. Yelena Yuriy Janjigian
    189 Janjigian
  22. Marc Ladanyi
    1041 Ladanyi
  23. Martin Henner Voss
    163 Voss
  24. Jamie Erin Chaft
    160 Chaft
  25. David G Pfister
    295 Pfister
  26. Gopakumar Vasudeva Iyer
    167 Iyer
  27. Shrujal S Baxi
    90 Baxi
  28. Richard J Wong
    250 Wong
  29. Gregory J Riely
    417 Riely
  30. Mrinal M Gounder
    109 Gounder
  31. Rona Denit Yaeger
    118 Yaeger
  32. Sandra Pierina D'Angelo
    138 D'Angelo
  33. Christopher Barker
    138 Barker
  34. Luc Morris
    149 Morris
  35. Charlotte Eielson Ariyan
    103 Ariyan
  36. Bernard Bochner
    359 Bochner
  37. Ahmet Zehir
    212 Zehir
  38. Alan Loh Ho
    119 Ho
  39. Michael Forman Berger
    497 Berger
  40. Howard Scher
    970 Scher
  41. William Douglas Tap
    176 Tap
  42. Matthew David Hellmann
    255 Hellmann
  43. Jonathan Eric Rosenberg
    296 Rosenberg
  44. Abraham Ari Hakimi
    181 Hakimi
  45. Jose T Baselga
    461 Baselga
  46. Charles Rudin
    228 Rudin
  47. Pedram Razavi
    60 Razavi
  48. Chung-Han   Lee
    60 Lee
  49. David   Barron
    11 Barron
  50. Emmet John Jordan
    43 Jordan
  51. Manuela F Berger
    5 Berger