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33 Role of plasma T-cell-derived circulating DNA level in anti-PD(L)1 immunotherapy in advanced stage non-small cell lung cancer
  1. Nuthchaya Mejun,
  2. Nophol Leelayuwatanakul,
  3. Pongsakorn Ouwongprayoon,
  4. Chanida Vinayanuwattikun and
  5. Nattiya Hirankarn
  1. Chulalongkorn University, Bangkok, Thailand


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.

Ethics Approval All methods were carried out in accordance with the declarations of Helsinki. The Institutional Review Board (IRB), Faculty of Medicine, Chulalongkorn University approved the study protocol (IRB 385/63).

Abstract 33 Table 1

Demographic characteristics of detectable plasma circulating DNA from 47 advanced NSCLC patients categorized by%ratio of T-cirDNA/cirDNA into undetectable, low (≤ 1%ratio) and high (> 1%ratio)

Abstract 33 Figure 1

A cumulative survival curve comparison of%ratio of T-cirDNA/cirDNA; undetectable, low and high by using overall survival (Kaplan–Meier method and Log rank test, p-value 0.071)

Abstract 33 Table 2

Univariate and multivariate analysis of prognostic factors by progression-free survival including demographic characteristics, treatment and%ratio of T-cirDNA/cirDNA using cox proportion hazards regression analysis

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