Background We previously published prognostic impact of T-cell-derived circulating DNA (T-cirDNA) and its correlation with intra-tumoral CD8 tumor-infiltrating lymphocyte (TIL) in advanced stage non-small cell lung cancer (NSCLC). Currently, PD-L1 staining is solely the standard biomarker of anti-PD-(L)1 immunotherapy treatment response. However, not perfect correlation in individual patient.
Methods We prospectively explored plasma T-cirDNA and cirDNA (total circulating DNA), using real-time PCR with Taqman assay-specific rearranged TCR-beta CDR3 region in 47 advanced NSCLC patients treated with anti-PD-(L)1 immunotherapy. We defined patients into undetectable, low (≤1% ratio) and high (>1% ratio) T-cirDNA/cirDNA based on previous study. Demographic characteristics such as sex, age, ECOG performance status, smoking, histology, PD-L1 staining, treatment regimen were integrated with T-cirDNA/cirDNA into the cox-regression analysis model.
Results Out of 47 patients, 60% of participants had detectable plasma T-cirDNA/cirDNA with a median of 0.03 [range 0–4.7] ngml-1(table 1). Undetectable group was significantly correlated with the longest overall survival (OS) with a median of 25.5 [range 8–73.7] months (p-value 0.05) (figure 1). Multivariate analysis of progression-free survival (PFS) revealed 0–1 ECOG performance status and undetectable T-cirDNA correlated with favorable outcome, hazard ratio (HR) of 0.05 [95% CI 0.007–0.4, p-value 0.005] and 0.1 [95% CI 0.01–0.7, p-value 0.02] respectively. High amount of circulating DNA which represented high tumor burden and mono-anti-PD-(L)1 immunotherapy were correlated with unfavorable disease control with the HR of 6.6 [95% CI 1.1–37.9, p-value 0.03] and 6.3 [95% CI 1.3–29.1, p-value 0.01] respectively. For detectable T-cirDNA group, high level correlated with better disease control than low level (HR 0.1 [95% CI 0.02–0.8, p-value 0.03]) (table 2). We did observe paradoxical effect in predictive implication in undetectable and high level of T-cirDNA/cirDNA%ratio.
Conclusions Incorporate with demographic characteristic, T-cell-derived circulating DNA could be adopted for predictive implication of anti-PD(L)1 immunotherapy usage.
Acknowledgements This research was supported by the National Research Council of Thailand (Grant number 347/2564) to CV and NH. Biospecimen collection was supported by Biobank, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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