Association between plasma somatic copy number variations and response to immunotherapy in patients with programmed death-ligand 1-negative non-small cell lung cancer

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.