Plasma D‐dimer and interleukin‐6 are associated with treatment response and progression‐free survival in advanced NSCLC patients on anti‐PD‐1 therapy

Background/Aims Response to therapy after using immune checkpoint inhibitors (ICIs) is unpredictable due to significant interindividual variation in efficacy among advanced non‐small cell lung cancer (NSCLC) patients. The current study centered on the identification of perivascular blood biomarkers for predicting the effectiveness of anti‐programmed cell death protein 1 (anti‐PD‐1) treatment and progression‐free survival (PFS) in advanced NSCLC patients, that could be applied to help determine how to change treatment plans therapeutic regimens for optimizing clinical benefits. Methods A comprehensive review of 100 advanced or recurrent NSCLC patients receiving anti‐PD‐1 therapy (Camrelizumab, pembrolizumab, sintilimab, or nivolumab) was conducted between January 2018 and April 2021 in Tianjin Medical University Cancer Hospital. The cutoff values of D‐dimer were selected from rom our previous study, and interleukin‐6 (IL‐6) was divided according to the median. Using computed tomography, tumor response was evaluated in accordance with the Response Assessment Criteria in Solid Tumors, version 1.1. Results High IL‐6 level in advanced NSCLC patients was predictive of low efficacy and a short PFS duration after anti‐PD‐1 therapy. An increased D‐dimer value of 981 ng/mL was significantly predictive of disease progression in NSCLC patients treated with anti‐PD‐1 and high D‐dimer expression predictive of short duration of PFS. Further studies on the correlation between IL‐6, D‐dimer, and anti‐PD‐1 efficacy in NSCLC patients stratified by gender revealed that D‐dimer and IL‐6 levels were significantly associated with the risk of PFS in male patients. Conclusions High IL‐6 content in peripheral blood in patients with advanced non‐small cell lung cancer may contribute to poor anti‐PD‐1 efficacy and short duration of PFS through inducing alterations in the tumor microenvironment. D‐dimer in peripheral blood is predictive of hyperfibrinolysis and contributes to the release of tumor‐driven specific factors, leading to poor effects of anti‐PD‐1 therapy.