Cargando…

Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies

BACKGROUND: Anti-programmed cell death 1 (PD-1) antibodies have demonstrated improved overall survival (OS) and progression-free survival (PFS) in a subset of patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). To date, no blood biomarkers have been identified in NSCLC t...

Descripción completa

Detalles Bibliográficos
Autores principales: Soyano, Aixa E., Dholaria, Bhagirathbhai, Marin-Acevedo, Julian A., Diehl, Nancy, Hodge, David, Luo, Yan, Manochakian, Rami, Chumsri, Saranya, Adjei, Alex, Knutson, Keith L., Lou, Yanyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251165/
https://www.ncbi.nlm.nih.gov/pubmed/30470260
http://dx.doi.org/10.1186/s40425-018-0447-2
_version_ 1783373062234701824
author Soyano, Aixa E.
Dholaria, Bhagirathbhai
Marin-Acevedo, Julian A.
Diehl, Nancy
Hodge, David
Luo, Yan
Manochakian, Rami
Chumsri, Saranya
Adjei, Alex
Knutson, Keith L.
Lou, Yanyan
author_facet Soyano, Aixa E.
Dholaria, Bhagirathbhai
Marin-Acevedo, Julian A.
Diehl, Nancy
Hodge, David
Luo, Yan
Manochakian, Rami
Chumsri, Saranya
Adjei, Alex
Knutson, Keith L.
Lou, Yanyan
author_sort Soyano, Aixa E.
collection PubMed
description BACKGROUND: Anti-programmed cell death 1 (PD-1) antibodies have demonstrated improved overall survival (OS) and progression-free survival (PFS) in a subset of patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). To date, no blood biomarkers have been identified in NSCLC to predict clinical outcomes of treatment with anti-PD-1 antibodies. PATIENT AND METHODS: We performed an analysis of retrospectively registered data of 157 patients with advanced NSCLC treated with anti-PD-1 antibodies at Mayo Clinic in Florida and Rochester. White blood cell count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), ANC to ALC (ANC: ALC) ratio, absolute eosinophil count, absolute monocyte count (AMC), platelet counts, and myeloid to lymphoid (M:L) ratio at baseline and throughout treatment were assessed. Kaplan-Meier method and Cox proportional hazards model were performed. RESULTS: We treated 146 patients with nivolumab and 11 with pembrolizumab between January 1, 2015 and April 15, 2017. At median follow-up of 20 months, median OS and PFS were 6.0 and 2.6 months, respectively. Higher baseline ANC, AMC, ANC: ALC ratio and M: L ratio correlated with worse clinical outcomes in patients who underwent anti-PD-1 treatment. A baseline ANC: ALC ratio of 5.9 or higher had a significantly increased risk of death (hazard ratio [HR] =1.94; 95% confidence interval [CI], 1.24–3.03; P = 0.004) and disease progression (HR, 1.65; 95% CI, 1.17–2.34; P = 0.005) compared with patients with lower ratio. Similarly, a baseline M: L ratio of 11.3 or higher had significantly increased risk of death (HR, 2.5; 95% CI, 1.54–4.05; P < 0.001), even after a multivariate analysis (HR, 2.31; P = 0.002), compared to those with lower ratio. CONCLUSIONS: Increased baseline ANC: ALC ratio and M: L ratio before initiation of anti-PD1 antibodies were associated with poor PFS and OS in advanced NSCLC patients. The potential predictive value of these readily available biomarkers might help with risk stratification and treatment strategies. These findings warrant further investigation in a larger, prospective study. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40425-018-0447-2) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6251165
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-62511652018-11-26 Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies Soyano, Aixa E. Dholaria, Bhagirathbhai Marin-Acevedo, Julian A. Diehl, Nancy Hodge, David Luo, Yan Manochakian, Rami Chumsri, Saranya Adjei, Alex Knutson, Keith L. Lou, Yanyan J Immunother Cancer Research Article BACKGROUND: Anti-programmed cell death 1 (PD-1) antibodies have demonstrated improved overall survival (OS) and progression-free survival (PFS) in a subset of patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). To date, no blood biomarkers have been identified in NSCLC to predict clinical outcomes of treatment with anti-PD-1 antibodies. PATIENT AND METHODS: We performed an analysis of retrospectively registered data of 157 patients with advanced NSCLC treated with anti-PD-1 antibodies at Mayo Clinic in Florida and Rochester. White blood cell count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), ANC to ALC (ANC: ALC) ratio, absolute eosinophil count, absolute monocyte count (AMC), platelet counts, and myeloid to lymphoid (M:L) ratio at baseline and throughout treatment were assessed. Kaplan-Meier method and Cox proportional hazards model were performed. RESULTS: We treated 146 patients with nivolumab and 11 with pembrolizumab between January 1, 2015 and April 15, 2017. At median follow-up of 20 months, median OS and PFS were 6.0 and 2.6 months, respectively. Higher baseline ANC, AMC, ANC: ALC ratio and M: L ratio correlated with worse clinical outcomes in patients who underwent anti-PD-1 treatment. A baseline ANC: ALC ratio of 5.9 or higher had a significantly increased risk of death (hazard ratio [HR] =1.94; 95% confidence interval [CI], 1.24–3.03; P = 0.004) and disease progression (HR, 1.65; 95% CI, 1.17–2.34; P = 0.005) compared with patients with lower ratio. Similarly, a baseline M: L ratio of 11.3 or higher had significantly increased risk of death (HR, 2.5; 95% CI, 1.54–4.05; P < 0.001), even after a multivariate analysis (HR, 2.31; P = 0.002), compared to those with lower ratio. CONCLUSIONS: Increased baseline ANC: ALC ratio and M: L ratio before initiation of anti-PD1 antibodies were associated with poor PFS and OS in advanced NSCLC patients. The potential predictive value of these readily available biomarkers might help with risk stratification and treatment strategies. These findings warrant further investigation in a larger, prospective study. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40425-018-0447-2) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-23 /pmc/articles/PMC6251165/ /pubmed/30470260 http://dx.doi.org/10.1186/s40425-018-0447-2 Text en © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Soyano, Aixa E.
Dholaria, Bhagirathbhai
Marin-Acevedo, Julian A.
Diehl, Nancy
Hodge, David
Luo, Yan
Manochakian, Rami
Chumsri, Saranya
Adjei, Alex
Knutson, Keith L.
Lou, Yanyan
Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies
title Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies
title_full Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies
title_fullStr Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies
title_full_unstemmed Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies
title_short Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies
title_sort peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung cancer patients treated with anti-pd-1 antibodies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251165/
https://www.ncbi.nlm.nih.gov/pubmed/30470260
http://dx.doi.org/10.1186/s40425-018-0447-2
work_keys_str_mv AT soyanoaixae peripheralbloodbiomarkerscorrelatewithoutcomesinadvancednonsmallcelllungcancerpatientstreatedwithantipd1antibodies
AT dholariabhagirathbhai peripheralbloodbiomarkerscorrelatewithoutcomesinadvancednonsmallcelllungcancerpatientstreatedwithantipd1antibodies
AT marinacevedojuliana peripheralbloodbiomarkerscorrelatewithoutcomesinadvancednonsmallcelllungcancerpatientstreatedwithantipd1antibodies
AT diehlnancy peripheralbloodbiomarkerscorrelatewithoutcomesinadvancednonsmallcelllungcancerpatientstreatedwithantipd1antibodies
AT hodgedavid peripheralbloodbiomarkerscorrelatewithoutcomesinadvancednonsmallcelllungcancerpatientstreatedwithantipd1antibodies
AT luoyan peripheralbloodbiomarkerscorrelatewithoutcomesinadvancednonsmallcelllungcancerpatientstreatedwithantipd1antibodies
AT manochakianrami peripheralbloodbiomarkerscorrelatewithoutcomesinadvancednonsmallcelllungcancerpatientstreatedwithantipd1antibodies
AT chumsrisaranya peripheralbloodbiomarkerscorrelatewithoutcomesinadvancednonsmallcelllungcancerpatientstreatedwithantipd1antibodies
AT adjeialex peripheralbloodbiomarkerscorrelatewithoutcomesinadvancednonsmallcelllungcancerpatientstreatedwithantipd1antibodies
AT knutsonkeithl peripheralbloodbiomarkerscorrelatewithoutcomesinadvancednonsmallcelllungcancerpatientstreatedwithantipd1antibodies
AT louyanyan peripheralbloodbiomarkerscorrelatewithoutcomesinadvancednonsmallcelllungcancerpatientstreatedwithantipd1antibodies