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

Laura Mezquita; Isabel Preeshagul; Edouard Auclin; Diana Saravia; Lizza Hendriks; Hira Rizvi; Wungki Park; Ernest Nadal; Patricia Martin-Romano; Jose C. Ruffinelli; Santiago Ponce; Clarisse Audigier-Valette; Simona Carnio; Felix Blanc-Durand; Paolo Bironzo; Fabrizio Tabbò; Maria Lucia Reale; Silvia Novello; Matthew D. Hellmann; Peter Sawan; Jeffrey Girshman; Andrew J. Plodkowski; Gerard Zalcman; Margarita Majem; Melinda Charrier; Marie Naigeon; Caroline Rossoni; Anna Paola Mariniello; Luis Paz-Ares; Anne Marie Dingemans; David Planchard; Nathalie Cozic; Lydie Cassard; Gilberto Lopes; Nathalie Chaput; Kathryn Arbour; Benjamin Besse

doi:10.1016/j.ejca.2021.03.011

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

Laura Mezquita, Isabel Preeshagul, Edouard Auclin, Diana Saravia, Lizza Hendriks, Hira Rizvi, Wungki Park, Ernest Nadal, Patricia Martin-Romano, Jose C. Ruffinelli, Santiago Ponce, Clarisse Audigier-Valette, Simona Carnio, Felix Blanc-Durand, Paolo Bironzo, Fabrizio Tabbò, Maria Lucia Reale, Silvia Novello, Matthew D. Hellmann, Peter SawanJeffrey Girshman, Andrew J. Plodkowski, Gerard Zalcman, Margarita Majem, Melinda Charrier, Marie Naigeon, Caroline Rossoni, Anna Paola Mariniello, Luis Paz-Ares, Anne Marie Dingemans, David Planchard, Nathalie Cozic, Lydie Cassard, Gilberto Lopes, Nathalie Chaput, Kathryn Arbour, Benjamin Besse

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

28 Citations (Scopus)

Résumé

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-CD16^low 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.

langue originale	Anglais
Pages (de - à)	211-220
Nombre de pages	10
journal	European Journal of Cancer
Volume	151
Les DOIs	https://doi.org/10.1016/j.ejca.2021.03.011
état	Publié - 1 juil. 2021

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10.1016/j.ejca.2021.03.011

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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., ... Besse, B. (2021). Predicting immunotherapy outcomes under therapy in patients with advanced NSCLC using dNLR and its early dynamics. European Journal of Cancer, 151, 211-220. https://doi.org/10.1016/j.ejca.2021.03.011

@article{01640d633a994f7088be9877f5092bf2,

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.",

keywords = "Biomarker, Immunotherapy, NSCLC, Neutrophils, dNLR",

author = "Laura Mezquita and Isabel Preeshagul and Edouard Auclin and Diana Saravia and Lizza Hendriks and Hira Rizvi and Wungki Park and Ernest Nadal and Patricia Martin-Romano and Ruffinelli, {Jose C.} and Santiago Ponce and Clarisse Audigier-Valette and Simona Carnio and Felix Blanc-Durand and Paolo Bironzo and Fabrizio Tabb{\`o} and Reale, {Maria Lucia} and Silvia Novello and Hellmann, {Matthew D.} and Peter Sawan and Jeffrey Girshman and Plodkowski, {Andrew J.} and Gerard Zalcman and Margarita Majem and Melinda Charrier and Marie Naigeon and Caroline Rossoni and Mariniello, {Anna Paola} and Luis Paz-Ares and Dingemans, {Anne Marie} and David Planchard and Nathalie Cozic and Lydie Cassard and Gilberto Lopes and Nathalie Chaput and Kathryn Arbour and Benjamin Besse",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",

year = "2021",

month = jul,

day = "1",

doi = "10.1016/j.ejca.2021.03.011",

language = "English",

volume = "151",

pages = "211--220",

journal = "European Journal of Cancer",

issn = "0959-8049",

}

Mezquita, L, Preeshagul, I, Auclin, E, Saravia, D, Hendriks, L, Rizvi, H, Park, W, Nadal, E, Martin-Romano, P, Ruffinelli, JC, Ponce, S, Audigier-Valette, C, Carnio, S, Blanc-Durand, F, Bironzo, P, Tabbò, F, Reale, ML, Novello, S, Hellmann, MD, Sawan, P, Girshman, J, Plodkowski, AJ, Zalcman, G, Majem, M, Charrier, M, Naigeon, M, Rossoni, C, Mariniello, AP, Paz-Ares, L, Dingemans, AM, Planchard, D, Cozic, N, Cassard, L, Lopes, G, Chaput, N, Arbour, K & Besse, B 2021, 'Predicting immunotherapy outcomes under therapy in patients with advanced NSCLC using dNLR and its early dynamics', European Journal of Cancer, VOL. 151, p. 211-220. https://doi.org/10.1016/j.ejca.2021.03.011

TY - JOUR

T1 - Predicting immunotherapy outcomes under therapy in patients with advanced NSCLC using dNLR and its early dynamics

AU - Mezquita, Laura

AU - Preeshagul, Isabel

AU - Auclin, Edouard

AU - Saravia, Diana

AU - Hendriks, Lizza

AU - Rizvi, Hira

AU - Park, Wungki

AU - Nadal, Ernest

AU - Martin-Romano, Patricia

AU - Ruffinelli, Jose C.

AU - Ponce, Santiago

AU - Audigier-Valette, Clarisse

AU - Carnio, Simona

AU - Blanc-Durand, Felix

AU - Bironzo, Paolo

AU - Tabbò, Fabrizio

AU - Reale, Maria Lucia

AU - Novello, Silvia

AU - Hellmann, Matthew D.

AU - Sawan, Peter

AU - Girshman, Jeffrey

AU - Plodkowski, Andrew J.

AU - Zalcman, Gerard

AU - Majem, Margarita

AU - Charrier, Melinda

AU - Naigeon, Marie

AU - Rossoni, Caroline

AU - Mariniello, Anna Paola

AU - Paz-Ares, Luis

AU - Dingemans, Anne Marie

AU - Planchard, David

AU - Cozic, Nathalie

AU - Cassard, Lydie

AU - Lopes, Gilberto

AU - Chaput, Nathalie

AU - Arbour, Kathryn

AU - Besse, Benjamin

PY - 2021/7/1

Y1 - 2021/7/1

N2 - 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.

AB - 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.

KW - Biomarker

KW - Immunotherapy

KW - NSCLC

KW - Neutrophils

KW - dNLR

UR - http://www.scopus.com/inward/record.url?scp=85106271256&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2021.03.011

DO - 10.1016/j.ejca.2021.03.011

M3 - Article

C2 - 34022698

AN - SCOPUS:85106271256

SN - 0959-8049

VL - 151

SP - 211

EP - 220

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -