Objective: To determine how patients with non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1)-negative and/or a low tumor mutation burden status benefit from immune checkpoint inhibitors (ICI).
Methods: We determined the plasma cell-free DNA profiles of 25 patients with PD-L1-negative advanced NSCLC before ICI therapy using low-coverage whole-genome sequencing.
Results: Elevated cell-free copy number variations (CNVs) were associated with progressive disease, with a cutoff CNV score of 0.10 evaluated with an area under the curve of 0.790 in PD-L1-negative NSCLC. CNV changes were also correlated with poor survival. Progression-free survival and overall survival were both significantly shorter in CNVhigh compared with CNVlow patients.
Conclusions: Cell-free CNV may be a useful peripheral blood biomarker for predicting the response to ICIs in patients with NSCLC.
Keywords: Immune checkpoint inhibitor; cell-free DNA; copy number variation; molecular immune response; non-small cell lung cancer; programmed death-ligand 1.