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
    215 Chan
  2. Paul Russo
    446 Russo
  3. Dean Bajorin
    404 Bajorin
  4. Robert Motzer
    744 Motzer
  5. Leonard B Saltz
    580 Saltz
  6. Ronald P DeMatteo
    597 DeMatteo
  7. Jedd D Wolchok
    656 Wolchok
  8. David Solit
    431 Solit
  9. Neil Howard Segal
    101 Segal
  10. Viviane S Tabar
    117 Tabar
  11. Ronglai Shen
    127 Shen
  12. Philip H Gutin
    152 Gutin
  13. Cameron Brennan
    151 Brennan
  14. Nadeem Riaz
    210 Riaz
  15. Geoffrey Yuyat Ku
    86 Ku
  16. Antonio Marcilio Padula Omuro
    176 Omuro
  17. Nancy Y. Lee
    547 Lee
  18. Naiyer A Rizvi
    156 Rizvi
  19. Zsofia Kinga Stadler
    144 Stadler
  20. Thomas Kaley
    82 Kaley
  21. Yelena Yuriy Janjigian
    145 Janjigian
  22. Marc Ladanyi
    863 Ladanyi
  23. Martin Henner Voss
    126 Voss
  24. Jamie Erin Chaft
    126 Chaft
  25. David G Pfister
    247 Pfister
  26. Gopakumar Vasudeva Iyer
    125 Iyer
  27. Shrujal S Baxi
    69 Baxi
  28. Richard J Wong
    228 Wong
  29. Gregory J Riely
    344 Riely
  30. Mrinal M Gounder
    68 Gounder
  31. Rona Denit Yaeger
    64 Yaeger
  32. Christopher Barker
    113 Barker
  33. Luc Morris
    123 Morris
  34. Charlotte Eielson Ariyan
    77 Ariyan
  35. Bernard Bochner
    324 Bochner
  36. Ahmet Zehir
    149 Zehir
  37. Alan Loh Ho
    79 Ho
  38. Michael Forman Berger
    380 Berger
  39. Howard Scher
    817 Scher
  40. William Douglas Tap
    122 Tap
  41. Matthew David Hellmann
    163 Hellmann
  42. Jonathan Eric Rosenberg
    218 Rosenberg
  43. Abraham Ari Hakimi
    129 Hakimi
  44. Jose T Baselga
    395 Baselga
  45. Charles Rudin
    161 Rudin
  46. Pedram Razavi
    24 Razavi
  47. Chung-Han   Lee
    37 Lee
  48. David   Barron
    7 Barron
  49. Emmet John Jordan
    29 Jordan
  50. Manuela F Berger
    5 Berger