WCLC 2025 - Posters & ePosters-P2.06.46 Multi-Omics Analysis Reveals Genomic Features Associated With Combination Immunotherapy Benefit in Advanced NSCLC

P2.06.46 Multi-Omics Analysis Reveals Genomic Features Associated With Combination Immunotherapy Benefit in Advanced NSCLC

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This study investigates genomic and transcriptomic factors associated with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients undergoing first-line combination immunotherapy (PD-1/PD-L1 blockade plus chemotherapy). A total of 54 patients were enrolled, with tissue biopsies from 45 and blood samples collected across treatment cycles for multi-omics profiling. Comprehensive genomic analysis using a 437-gene panel and RNA sequencing were conducted to identify biomarkers predictive of treatment benefit.<br /><br />Key findings include the association of LRP1B mutations with longer progression-free survival (PFS), while FBXW7 mutations correlated with shorter PFS and poorer outcomes. FBXW7-mutated tumors showed increased tumor proliferation and suppressed immune signaling pathways, including reduced IFN-α and IFN-γ responses, alongside decreased infiltration of CD4 memory T cells and natural killer (NK) cells. Transcriptomic profiling revealed that low expression of SPP1, a gene involved in CD8 T cell suppression and tumor immune evasion, was linked to significantly longer PFS.<br /><br />Dynamic monitoring of circulating tumor DNA (ctDNA) revealed that detectable ctDNA during treatment was a strong predictor of worse PFS at several treatment points. Conversely, patients who achieved early clearance of ctDNA demonstrated markedly improved PFS outcomes.<br /><br />This prospective multi-omics study highlights important genomic features—particularly the mutation status of LRP1B and FBXW7—and ctDNA dynamics that correlate with immunotherapy efficacy in advanced NSCLC. These findings provide insight into the tumor microenvironment and immune interactions influencing treatment response, offering potential predictive biomarkers to better guide therapeutic strategies.

Asset Subtitle

Lailing Li

Meta Tag

Speaker Lailing Li

Topic Pathology and Biomarkers

Keywords

non-small cell lung cancer

NSCLC

immunotherapy

PD-1 blockade

PD-L1 blockade

LRP1B mutation

FBXW7 mutation

circulating tumor DNA

progression-free survival

tumor microenvironment