Noninvasive early identification of therapeutic benefit from immune checkpoint inhibition Journal Article

   


Authors: Nabet, B. Y.; Esfahani, M. S.; Moding, E. J.; Hamilton, E. G.; Chabon, J. J.; Rizvi, H.; Steen, C. B.; Chaudhuri, A. A.; Liu, C. L.; Hui, A. B.; Almanza, D.; Stehr, H.; Gojenola, L.; Bonilla, R. F.; Jin, M. C.; Jeon, Y. J.; Tseng, D.; Liu, C.; Merghoub, T.; Neal, J. W.; Wakelee, H. A.; Padda, S. K.; Ramchandran, K. J.; Das, M.; Plodkowski, A. J.; Yoo, C.; Chen, E. L.; Ko, R. B.; Newman, A. M.; Hellmann, M. D.; Alizadeh, A. A.; Diehn, M.
Article Title: Noninvasive early identification of therapeutic benefit from immune checkpoint inhibition
Abstract: Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs. © 2020 Elsevier Inc. Multiparameter noninvasive models that integrate pre-treatment ctDNA and peripheral immune features, together with early on-treatment ctDNA dynamics, show promise in predicting durable clinical response to immune checkpoint blockade treatment in patients with non-small cell lung cancer. © 2020 Elsevier Inc.
Keywords: immunotherapy; non-small cell lung cancer; circulating tumor dna; liquid biopsy; immune checkpoint inhibition; response classification
Journal Title: Cell
Volume: 183
Issue: 2
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2020-10-15
Start Page: 363
End Page: 376.e13
Language: English
DOI: 10.1016/j.cell.2020.09.001
PUBMED: 33007267
PROVIDER: scopus
PMCID: PMC7572899
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85092497602&doi=10.1016%2fj.cell.2020.09.001&partnerID=40&md5=c8393746f99a8c05a3fdb11826795fbc
Notes: Article -- Export Date: 2 November 2020 -- Source: Scopus
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MSK Authors
  1. Taha Merghoub
    365 Merghoub
  2. Cailian Liu
    60 Liu
  3. Matthew David Hellmann
    412 Hellmann
  4. Andrew Joseph Plodkowski
    116 Plodkowski
  5. Hira Abbas Rizvi
    123 Rizvi
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