Association of Dynamic Changes inPeripheral Blood Indexes With Response to PD-1 Inhibitor-Based Combination Therapy and Survival Among Patients With Advanced Non-Small Cell Lung Cancer.

Yuzhong Chen,Wei Zhu,Yuan Wu,Jingwei Xia,Shaodi Wen,Banzhou Pan,Bo Shen,Xiaoyue Du

doi:10.3389/fimmu.2021.672271

Abstract

BackgroundPD-1 inhibitors have been routinely used in the treatment of advanced non-small cell lung cancer (NSCLC), and have demonstrated to significantly improve survivorship when combining with other conventional therapies, such as chemotherapy and anti-angiogenesis therapy. PD-L1 is the most commonly used biomarker to select benefiting groups, while not all patients with high PD-L1 expression benefit from immunotherapy. Therefore, identifying other prognostic and predictive biomarkers, including peripheral blood indexes, is essential.MethodsWe retrospectively collected medical records and hematological data of 151 patients with advanced NSCLC treated with PD-1 inhibitor-based combination therapy in our hospital. The peripheral blood indexes of interest were NLR, PLR, PAR, Hb, LDH, CEA, and NSE. The association between peripheral blood indexes and treatment responses or survival outcomes was examined by multivariable logistic regression and Cox regression, respectively.ResultsThe decreased CEA at week 6 (OR = 4.209, 95%CI: 1.287-13.758) or 12 (OR = 7.267, 95%CI: 1.508-35.006) post-treatment was related to a higher disease control rate. The decrease or NLR at week 6 (OR = 3.081, 95%CI: 1.464-6.483) or 12 (OR = 3.304, 95%CI: 1.560-7.001) post-treatment, or CEA at week 12 post-treatment (OR = 2.469, 95%CI: 1.134-5.375), was associated with a higher objective response rate. Patients whose NLR (HR = 0.610, 95%CI: 0.411-0.907) or CEA (HR = 0.477, 95%CI: 0.320-0.710) decreased at week 6 post-treatment tended to have longer progression-free survival, and similar results were found in those with decreased NLR (HR = 0.587, 95%CI: 0.388-0.886) or CEA (HR = 0.406, 95%CI: 0.270-0.609) at week 12 post-treatment. Patients whose CEA (HR = 0.543, 95%CI: 0.339-0.871) or NSE (HR = 0.619, 95%CI: 0.386-0.994) decreased after 6 weeks post-treatment appeared to have longer overall survival, and the same was found for those whoseCEA (HR = 0.620, 95%CI: 0.390-0.986) or NSE (HR = 0.578, 95%CI: 0.353-0.947) was decreased at 12 weeks after treatment.ConclusionPost-treatment NLR, CEA and NSE changes are suggestive indicators for the prognosis of NSCLC patients after immunotherapy.

Highlights

Immunotherapy, especially immune checkpoint inhibitors (ICIs) represented by programmed cell death protein-1 (PD-1) inhibitors, has significantly improved the prognosis of patients with advanced non-small cell lung cancer (NSCLC)
Based on the Cox regression analysis (Tables 4, 5, only significant variables from univariable analysis are shown), we found that Eastern Cooperative Oncology Group performance status (ECOG PS) (0 vs. 2: 11.2m vs. 4.1m, HR = 0.160, 95% CI: 0.050-0.515; 1 vs. 2: 7.9m vs. 4.1m, HR = 0.217, 95%CI: 0.0770.612), radiotherapy (Yes vs. No: 11.2m vs. 7.2m, HR = 0.536, 95%CI: 0.359-0.800), NLR6w (Down vs. Up: 11.2m vs. 7.2m, HR = 0.610, 95%CI: 0.411-0.907), CEA6w (Down vs. Up: 10.5m vs. 6.6m, HR = 0.477, 95%CI: 0.320-0.710), NLR12w (Down vs. Up: 10.8m vs. 5.9m, HR = 0.587, 95%CI: 0.388-0.886) and CEA12w (Down vs. Up: 11.2m vs. 6.0m, HR = 0.406, 95%CI: 0.270-0.609) were independently associated with progression-free survival (PFS) (Figure 2)
This is the first study to assess the association between peripheral blood markers and the outcome of progressive disease (PD)-1 inhibitor-based combination therapy in a Chinese population, and our data can provide the basis for stratification in later RCTs

Summary

Introduction

Immunotherapy, especially immune checkpoint inhibitors (ICIs) represented by programmed cell death protein-1 (PD-1) inhibitors, has significantly improved the prognosis of patients with advanced non-small cell lung cancer (NSCLC). A certain percentage of patients with negative PD-L1 expression or low TMB can still benefit from immunotherapy. Oncogenic alterations, such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), are usually associated with poor treatment response. PD-1 inhibitors have been routinely used in the treatment of advanced nonsmall cell lung cancer (NSCLC), and have demonstrated to significantly improve survivorship when combining with other conventional therapies, such as chemotherapy and anti-angiogenesis therapy. Identifying other prognostic and predictive biomarkers, including peripheral blood indexes, is essential

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Conclusion