Correlations between peripheral blood biomarkers and clinical outcomes in advanced non-small cell lung cancer patients who received immunotherapy-based treatments

Yuequan Shi; Xiaoyan Liu; Jia Liu; Dongming Zhang; Xiangning Liu; Yuan Yue; Qing Zhou; Xiaoxing Gao; Minjiang Chen; Yan Xu; Jing Zhao; Wei Zhong; Mariano Provencio; Jacek Jassem; Terence M Williams; Andreas Seeber; Florian Kocher; Mengzhao Wang

doi:10.21037/tlcr-21-710

Correlations between peripheral blood biomarkers and clinical outcomes in advanced non-small cell lung cancer patients who received immunotherapy-based treatments

Transl Lung Cancer Res. 2021 Dec;10(12):4477-4493. doi: 10.21037/tlcr-21-710.

Authors

Yuequan Shi¹, Xiaoyan Liu¹, Jia Liu¹, Dongming Zhang¹, Xiangning Liu¹, Yuan Yue¹, Qing Zhou¹, Xiaoxing Gao¹, Minjiang Chen¹, Yan Xu¹, Jing Zhao¹, Wei Zhong¹, Mariano Provencio², Jacek Jassem³, Terence M Williams⁴, Andreas Seeber⁵, Florian Kocher⁵, Mengzhao Wang¹

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
² Medical Oncology Department, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
³ Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.
⁴ Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, USA.
⁵ Department of Internal Medicine V (Hematology and Oncology), Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Innsbruck, Austria.

Abstract

Background: Peripheral blood-based biomarkers (PBB) predicting response, survival and immune-related adverse events (irAEs) in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are still a matter of debate. Thus, we investigated the associations between PBB, the efficacy of ICIs and the incidence of irAEs.

Methods: Patients with advanced NSCLC, who had been treated at Peking Union Medical College Hospital and received ICIs or chemoimmunotherapy from January 2015 to December 2020, were retrospectively identified. PBBs results were retrieved from medical records. Associations with overall response rate, survival, and incidence of irAEs were assessed using Kruskal-Wallis, Kaplan-Meier analysis, Pearson's chi-squared and Student's t-tests as required. Cox proportional hazards and logistic regression models were used to determine independent risk factors. Analyses were performed on the whole population (n=103), patients receiving ICIs only (n=32), and patients receiving chemoimmunotherapy (n=71). Changes in pretreatment and on-treatment PBB were also analyzed.

Results: Among 103 patients, 38 (36.9%) developed irAEs. Pretreatment absolute lymphocyte count (ALC) was related to an increased risk of irAEs in the whole population [odds ratio (OR), 2.165; 95% confidence interval (CI): 1.040 to 4.509, P=0.039] and patients receiving ICIs only (OR, 6.461; 95% CI: 1.067 to 39.112; P=0.042). A low prognostic nutritional index (PNI ≤45) was associated with worse progression-free survival (PFS) and overall survival (OS) in the whole population, in patients receiving ICIs only, and in patients receiving chemoimmunotherapy. High pretreatment interleukin (IL)-6 was associated with both worse PFS and OS in the whole population (IL-6 >13.80 pg/mL), in patients receiving ICIs only (IL-6 >11.30 pg/mL), and in patients receiving chemoimmunotherapy (IL-6 >11.85 pg/mL). Increase of IL-6 during treatment was associated with inferior OS in the whole population (P<0.001).

Conclusions: Pretreatment ALC has the potential to predict irAEs in patients with advanced NSCLC treated with ICIs. Additionally, a low level of pretreatment PNI and high level of IL-6 may be associated with shorter survival.

Keywords: Immune checkpoint inhibitors (ICIs); advanced non-small cell lung cancer (NSCLC); immune-related adverse events (irAEs); peripheral blood biomarker.