MAR 30, 2023 1:00 PM +08

TCR repertoire profiling to predict NSCLC response to immunotherapy - feasibility study

C.E. Credits: P.A.C.E. CE Florida CE


The circulating T-cell receptor (TCR) repertoire is a dynamic representation of overall immune responses in an individual. Here we aimed to correlate pre-treatment circulating TCR repertoire metrics and clinical outcome in advanced non-small cell lung cancer (NSCLC). We prospectively collected baseline blood from patients treated with first-line pembrolizumab monotherapy (n=53) or in combination with chemotherapy (n=48). TCR-β repertoire was assessed using the Oncomine TCR Beta-SR Assay and correlated with clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS) and immune-related adverse events (irAEs). We observed an association between reduced number of unique clones and improved CBR among patients in treated with pembrolizumab (RR=2.86, 95%CI 1.04-8.73, P=0.039). However, there was no statistically significant correlation between TCR repertoire and PFS or OS. In patients in treated with pembrolizumab plus chemotherapy, increased number of unique clones (HR=2.96, 95%CI 1.28-6.88, P=0.012) and Shannon Diversity (HR=2.73, 95%CI 1.08-6.87, P=0.033); and reduced evenness (HR=0.43, 95%CI 0.21-0.90, P= 0.025) and convergence (HR= 0.41, 95%CI 0.19-0.90, P=0.027) were associated with improved PFS. Only increased number of unique clones (HR= 4.62, 95%CI 1.52-14.02, P=0.007) was associated with improved OS. A logistic regression model score combining the TCR repertoire metrics improved the prediction of CBR (RR=0.52,95%CI 0.24-0.84, P=0.006) and was strongly associated with OS (HR=0.20, 95%CI 0.05-0.76, P<0.0001). Reduced TCR conversion was associated with increased frequency of irAEs needing systemic steroid treatment. Overall, pre-treatment TCR repertoire might serve as a predictive biomarker for clinical outcomes among patients with advanced NSCLC treated with anti-PD1, in particular for those receiving combination therapy.

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