2023 World Conference on Lung Cancer (Posters)-P2.05. Prediction of Durable Response to Immunotherapy by Early Dynamic in ctDNA and Peripheral Immune Features in NSCLC

P2.05. Prediction of Durable Response to Immunotherapy by Early Dynamic in ctDNA and Peripheral Immune Features in NSCLC - PDF(Abstract)

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A prospective clinical trial was conducted to establish and validate a model for predicting the response to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients. The study included EGFR and ALK mutation-negative advanced NSCLC patients treated with ICIs as a first-line therapy. Pre-treatment and early on-treatment circulating tumor DNA (ctDNA) were collected for genetic sequencing, and pre-treatment peripheral blood mononuclear cells were collected for RNA sequencing. The ctDNA levels, peripheral immune features, and ctDNA dynamics during treatment were integrated into a multiparameter Bayesian framework to predict the response to ICIs.<br /><br />A total of 104 NSCLC patients were recruited, and most had stage IV disease and adenocarcinoma. The cohort was randomly split into a discovery cohort and a validation cohort. The model showed that higher ctDNA level-normalized bTMB (blood tumor mutational burden) prior to ICI therapy and a greater reduction in ctDNA concentration during early stages of treatment were associated with a durable clinical benefit (DCB). The model also found no significant difference in circulating CD8 T cells between patients with non-durable benefit (NDB) and DCB. The model predicted the DCB with a sensitivity of 100% and specificity of 84.2% in the discovery cohort, and a sensitivity of 78.6% and specificity of 86.7% in the validation cohort.<br /><br />In conclusion, this study developed a noninvasive model that can reliably predict the durable response to ICI therapy in NSCLC patients by integrating pre-treatment ctDNA, peripheral immune features, and early on-treatment ctDNA dynamics. This model has the potential to provide early prediction of outcomes for NSCLC patients receiving ICIs, allowing for personalized treatment decisions.

Asset Subtitle

Xinghao Ai

Meta Tag

Speaker Xinghao Ai

Topic Metastatic NSCLC: Immunotherapy - Biomarker

Keywords

clinical trial

immune checkpoint inhibitors

non-small cell lung cancer

NSCLC

EGFR mutation

ALK mutation

circulating tumor DNA

ctDNA

peripheral blood mononuclear cells

RNA sequencing