Abstract 1044: Cell-free DNA concentration as a prognostic biomarker in patients with non-small cell lung cancer under immunotherapy treatment

The irruption of the immunotherapy for the treatment of non-small cell lung cancer (NSCLC) based on Immune Checkpoint Inhibitors (ICI) PD-1 and PD-L1 inhibitors is considered a treatment revolution. However, only a small percentage of patients benefit with ICI treatment over the long term, and precise biomarkers that can recognize these individuals before or early during treatment have so far eluded. PD-L1 expression and tumor mutational burden (TMB) are the most well studied biomarkers for predicting response to PD- (L)1 blockade-based ICI prior to treatment. TMB is still being clinically assessed whereas PD-L1 has several drawbacks for prediction of persistent benefit. Our aim is to evaluate the basal state and dynamic changes of cell-free DNA (cfDNA) concentration to predict and monitor response in NSCLC patients starting ICI. A total of 248 cfDNA concentration measurements were performed from 87 NSCLC patients. The quantification was done before the start of the treatment, at the second ICI cycle, after 6 and 12 months in treatment, and at progression if it was within the first 12 months. Quality and quantity of the cfDNA was assessed using Qubit High Sensitivity and Bioanalyzer 2100. We first explored the association with response of the basal cell-free DNA concentration using Mann-Whitney-Wilcoxon test. The longitudinal analysis between different time points was tested with Wilcoxon signed-rank tests. Response was ascertained using RECIST parameters at 3, 6, and 12 months. We evaluated the utility of the cfDNA concentration as a prognostic factor using Mantel-Cox test. The response association results indicate that early and long-term response is associated with lower levels of basal cfDNA (p