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(Slides)

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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 patients with advanced non-small cell lung cancer (NSCLC). The study collected pre-treatment and early on-treatment circulating tumor DNA (ctDNA) for genetic sequencing and peripheral blood mononuclear cells for RNA sequencing. The data from ctDNA and peripheral immune features, as well as the dynamics of ctDNA during treatment, were integrated using a multiparameter Bayesian framework to predict the response to ICIs.<br /><br />The results showed that the model could reliably predict the durable response to ICI therapy in NSCLC patients. Patients who had a longer progression-free survival (PFS) of more than 6 months (durable clinical benefit, DCB) had higher levels of ctDNA-normalized blood tumor mutational burden (bTMB) before ICI therapy and a greater reduction in ctDNA concentration during early stages of treatment. There were no significant differences in circulating CD8 T cells between patients with non-durable benefit (NDB) and those with disease progression in less than 6 months (NDB).<br /><br />The integrated model achieved 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 for predicting DCB. This noninvasive approach using ctDNA and peripheral immune features could potentially serve as an early identification tool for therapeutic benefit from immune checkpoint inhibition in NSCLC patients.<br /><br />This study provides valuable insights into predicting the response to immunotherapy in NSCLC patients, which can help guide treatment decisions and improve patient outcomes. Further research and validation of this model are needed to fully establish its clinical utility.

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

ctDNA

genetic sequencing

RNA sequencing

progression-free survival

blood tumor mutational burden

circulating CD8 T cells

immunotherapy