Predicting immunotherapy outcomes under therapy in patients with advanced NSCLC using dNLR and its early dynamics Journal Article

  


Authors: Mezquita, L.; Preeshagul, I.; Auclin, E.; Saravia, D.; Hendriks, L.; Rizvi, H.; Park, W.; Nadal, E.; Martin-Romano, P.; Ruffinelli, J. C.; Ponce, S.; Audigier-Valette, C.; Carnio, S.; Blanc-Durand, F.; Bironzo, P.; Tabbò, F.; Reale, M. L.; Novello, S.; Hellmann, M. D.; Sawan, P.; Girshman, J.; Plodkowski, A. J.; Zalcman, G.; Majem, M.; Charrier, M.; Naigeon, M.; Rossoni, C.; Mariniello, A.; Paz-Ares, L.; Dingemans, A. M.; Planchard, D.; Cozic, N.; Cassard, L.; Lopes, G.; Chaput, N.; Arbour, K.; Besse, B.
Article Title: Predicting immunotherapy outcomes under therapy in patients with advanced NSCLC using dNLR and its early dynamics
Abstract: Background: dNLR at the baseline (B), defined by neutrophils/[leucocytes-neutrophils], correlates with immune-checkpoint inhibitor (ICI) outcomes in advanced non–small-cell lung cancer (aNSCLC). However, dNLR is dynamic under therapy and its longitudinal assessment may provide data predicting efficacy. We sought to examine the impact of dNLR dynamics on ICI efficacy and understand its biological significance. Patients and methods: aNSCLC patients receiving ICI at 17 EU/US centres were included [Feb/13-Jun/18]. As chemotherapy-only group was evaluated (NCT02105168). dNLR was determined at (B) and at cycle2 (C2) [dNLR≤3 = low]. B+C2 dNLR were combined in one score: good = low (B+C2), poor = high (B+C2), intermediate = other situations. In 57 patients, we prospectively explored the immunophenotype of circulating neutrophils, particularly the CD15+CD244-CD16low cells (immature) by flow cytometry. Results: About 1485 patients treatment with ICI were analysed. In ICI-treated patients, high dNLR (B) (~1/3rd) associated with worse progression-free (PFS)/overall survival (OS) (HR 1.56/HR 2.02, P < 0.0001) but not with chemotherapy alone (N = 173). High dNLR at C2 was associated with worse PFS/OS (HR 1.64/HR 2.15, P < 0.0001). When dNLR at both time points were considered together, those with persistently high dNLR (23%) had poor survival (mOS = 5 months (mo)), compared with high dNLR at one time point (22%; mOS = 9.2mo) and persistently low dNLR (55%; mOS = 18.6mo) (P < 0.0001). The dNLR impact remained significant after PD-L1 adjustment. By cytometry, high rate of immature neutrophils (B) (30/57) correlated with poor PFS/OS (P = 0.04; P = 0.0007), with a 12-week death rate of 49%. Conclusion: The dNLR (B) and its dynamics (C2) under ICI associate with ICI outcomes in aNSCLC. Persistently high dNLR (B+C2) correlated with early ICI failure. Immature neutrophils may be a key subpopulation on ICI resistance. © 2021 Elsevier Ltd
Keywords: immunotherapy; biomarker; neutrophils; nsclc; dnlr
Journal Title: European Journal of Cancer
Volume: 151
ISSN: 0959-8049
Publisher: Elsevier Inc.  
Date Published: 2021-07-01
Start Page: 211
End Page: 220
Language: English
DOI: 10.1016/j.ejca.2021.03.011
PROVIDER: scopus
PUBMED: 34022698
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85106271256&doi=10.1016%2fj.ejca.2021.03.011&partnerID=40&md5=00516ee17cd96c45899c3daa8fdbf028
Notes: Article -- Export Date: 1 June 2021 -- Source: Scopus
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MSK Authors
  1. Matthew David Hellmann
    412 Hellmann
  2. Andrew Joseph Plodkowski
    114 Plodkowski
  3. Jeffrey Girshman
    31 Girshman
  4. Kathryn Cecilia Arbour
    89 Arbour
  5. Hira Abbas Rizvi
    123 Rizvi
  6. Peter Sawan
    20 Sawan
  7. Isabel Ruth Preeshagul
    39 Preeshagul
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