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:
Notes: Letter -- Export Date: 1 March 2019 -- Source: Scopus
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MSK Authors
  1. Timothy Chan
    317 Chan
  2. Paul Russo
    567 Russo
  3. Dean Bajorin
    637 Bajorin
  4. Robert Motzer
    1172 Motzer
  5. Leonard B Saltz
    760 Saltz
  6. Ronald P DeMatteo
    636 DeMatteo
  7. Jedd D Wolchok
    898 Wolchok
  8. David Solit
    729 Solit
  9. Neil Howard Segal
    189 Segal
  10. Viviane S Tabar
    206 Tabar
  11. Ronglai Shen
    192 Shen
  12. Philip H Gutin
    163 Gutin
  13. Cameron Brennan
    212 Brennan
  14. Nadeem Riaz
    374 Riaz
  15. Geoffrey Yuyat Ku
    207 Ku
  16. Antonio Marcilio Padula Omuro
    204 Omuro
  17. Nancy Y. Lee
    795 Lee
  18. Naiyer A Rizvi
    166 Rizvi
  19. Zsofia Kinga Stadler
    361 Stadler
  20. Thomas Kaley
    142 Kaley
  21. Yelena Yuriy Janjigian
    349 Janjigian
  22. Marc Ladanyi
    1277 Ladanyi
  23. Martin Henner Voss
    268 Voss
  24. Jamie Erin Chaft
    256 Chaft
  25. David G Pfister
    366 Pfister
  26. Gopakumar Vasudeva Iyer
    288 Iyer
  27. Shrujal S Baxi
    103 Baxi
  28. Richard J Wong
    370 Wong
  29. Gregory J Riely
    571 Riely
  30. Mrinal M Gounder
    207 Gounder
  31. Rona Denit Yaeger
    263 Yaeger
  32. Sandra Pierina D'Angelo
    229 D'Angelo
  33. Christopher Barker
    196 Barker
  34. Luc Morris
    248 Morris
  35. Charlotte Eielson Ariyan
    140 Ariyan
  36. Bernard Bochner
    444 Bochner
  37. Ahmet Zehir
    336 Zehir
  38. Alan Loh Ho
    209 Ho
  39. Michael Forman Berger
    701 Berger
  40. Howard Scher
    1110 Scher
  41. William Douglas Tap
    310 Tap
  42. Matthew David Hellmann
    405 Hellmann
  43. Jonathan Eric Rosenberg
    461 Rosenberg
  44. Abraham Ari Hakimi
    295 Hakimi
  45. Jose T Baselga
    483 Baselga
  46. Charles Rudin
    432 Rudin
  47. Pedram Razavi
    142 Razavi
  48. Chung-Han   Lee
    145 Lee
  49. David   Barron
    11 Barron
  50. Emmet John Jordan
    47 Jordan
  51. Manuela F Berger
    7 Berger