Genomic features of response to combination immunotherapy in patients with advanced non-small-cell lung cancer Journal Article


Authors: Hellmann, M. D.; Nathanson, T.; Rizvi, H.; Creelan, B. C.; Sanchez-Vega, F.; Ahuja, A.; Ni, A.; Novik, J. B.; Mangarin, L. M. B.; Abu-Akeel, M.; Liu, C.; Sauter, J. L.; Rekhtman, N.; Chang, E.; Callahan, M. K.; Chaft, J. E.; Voss, M. H.; Tenet, M.; Li, X. M.; Covello, K.; Renninger, A.; Vitazka, P.; Geese, W. J.; Borghaei, H.; Rudin, C. M.; Antonia, S. J.; Swanton, C.; Hammerbacher, J.; Merghoub, T.; McGranahan, N.; Snyder, A.; Wolchok, J. D.
Article Title: Genomic features of response to combination immunotherapy in patients with advanced non-small-cell lung cancer
Abstract: Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole-exome sequencing to examine non-small-cell lung cancer (NSCLC) treated with PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB) predicted improved objective response, durable benefit, and progression-free survival. TMB was independent of PD-L1 expression and the strongest feature associated with efficacy in multivariable analysis. The low response rate in TMB low NSCLCs demonstrates that combination immunotherapy does not overcome the negative predictive impact of low TMB. This study demonstrates the association between TMB and benefit to combination immunotherapy in NSCLC. TMB should be incorporated in future trials examining PD-(L)1 with CTLA-4 blockade in NSCLC. Hellmann et al. examine non-small-cell lung cancers treated with combined PD-1 and CTLA-4 blockade using whole-exome sequencing and find that high tumor mutation burden is the strongest feature associated with improved objective response, durable benefit, and progression-free survival in multivariable analysis. © 2018 Francis Crick Institute
Keywords: lung cancer; immunotherapy; ctla-4; pd-1; mutation burden; tmb
Journal Title: Cancer Cell
Volume: 33
Issue: 5
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2018-05-14
Start Page: 843
End Page: 852.e4
Language: English
DOI: 10.1016/j.ccell.2018.03.018
PROVIDER: scopus
PMCID: PMC5953836
PUBMED: 29657128
DOI/URL:
Notes: Article -- Export Date: 1 June 2018 -- Source: Scopus
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MSK Authors
  1. Natasha Rekhtman
    210 Rekhtman
  2. Jedd D Wolchok
    656 Wolchok
  3. Taha Merghoub
    201 Merghoub
  4. Martin Henner Voss
    126 Voss
  5. Jamie Erin Chaft
    126 Chaft
  6. Margaret Kathleen Callahan
    102 Callahan
  7. Cailian Liu
    33 Liu
  8. Matthew David Hellmann
    163 Hellmann
  9. Charles Rudin
    161 Rudin
  10. Ai   Ni
    47 Ni
  11. Hira Abbas Rizvi
    19 Rizvi
  12. Jennifer Lynn Sauter
    18 Sauter
  13. Megan Alexandra Tenet
    3 Tenet