Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies
Abstract 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...
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doaj-11ea289281944b548836e778645493702020-11-25T02:16:19ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262018-11-01611910.1186/s40425-018-0447-2Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodiesAixa E. Soyano0Bhagirathbhai Dholaria1Julian A. Marin-Acevedo2Nancy Diehl3David Hodge4Yan Luo5Rami Manochakian6Saranya Chumsri7Alex Adjei8Keith L. Knutson9Yanyan Lou10Department of Hematology and Oncology, Mayo ClinicDepartment of Hematology and Oncology, Mayo ClinicDepartment of Internal Medicine, Mayo ClinicDepartment of Biomedical Statistics and Informatics, Mayo ClinicDepartment of Biomedical Statistics and Informatics, Mayo ClinicDepartment of Cancer Biology, Mayo ClinicDepartment of Hematology and Oncology, Mayo ClinicRobert and Monica Jacoby Center for Breast Health, Mayo ClinicDepartment of Medical Oncology, Mayo ClinicDepartment of Cancer Biology, Mayo ClinicDepartment of Hematology and Oncology, Mayo ClinicAbstract 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.http://link.springer.com/article/10.1186/s40425-018-0447-2Non-small cell lung cancerNivolumabPembrolizumabAnti-PD-1ImmunotherapyRelapse/progression |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aixa E. Soyano Bhagirathbhai Dholaria Julian A. Marin-Acevedo Nancy Diehl David Hodge Yan Luo Rami Manochakian Saranya Chumsri Alex Adjei Keith L. Knutson Yanyan Lou |
spellingShingle |
Aixa E. Soyano Bhagirathbhai Dholaria Julian A. Marin-Acevedo Nancy Diehl David Hodge Yan Luo Rami Manochakian Saranya Chumsri Alex Adjei Keith L. Knutson Yanyan Lou Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies Journal for ImmunoTherapy of Cancer Non-small cell lung cancer Nivolumab Pembrolizumab Anti-PD-1 Immunotherapy Relapse/progression |
author_facet |
Aixa E. Soyano Bhagirathbhai Dholaria Julian A. Marin-Acevedo Nancy Diehl David Hodge Yan Luo Rami Manochakian Saranya Chumsri Alex Adjei Keith L. Knutson Yanyan Lou |
author_sort |
Aixa E. Soyano |
title |
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_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_sort |
peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung cancer patients treated with anti-pd-1 antibodies |
publisher |
BMJ Publishing Group |
series |
Journal for ImmunoTherapy of Cancer |
issn |
2051-1426 |
publishDate |
2018-11-01 |
description |
Abstract 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. |
topic |
Non-small cell lung cancer Nivolumab Pembrolizumab Anti-PD-1 Immunotherapy Relapse/progression |
url |
http://link.springer.com/article/10.1186/s40425-018-0447-2 |
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