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

Abstract

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.

Keywords: D-dimer; IL-6; NSCLC.