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. 2023 Dec 4:3:100130.
doi: 10.1016/j.jlb.2023.100130. eCollection 2024 Mar.

Plasma cell-free RNA PD-L1 or tissue PD-L1 protein expression and outcomes with first-line immunotherapy in metastatic non-small cell lung cancer

Paul R Walker  1   2 , Sriraksha Jayananda  1 , Melisa Pasli  3 , Mahvish Muzaffar  1
Affiliations

Plasma cell-free RNA PD-L1 or tissue PD-L1 protein expression and outcomes with first-line immunotherapy in metastatic non-small cell lung cancer

Paul R Walker et al. J Liq Biopsy. .

Abstract

Background: Tissue programmed death ligand-1 (PD-L1) protein expression is associated with immune checkpoint inhibitor (ICI) treatment benefit in metastatic non-small cell lung cancer (NSCLC). However, tissue PD-L1 protein testing is limited by sampling tumor heterogeneity and fraught with tissue acquisition difficulties. A liquid biopsy-based PD-L1 assay could overcome these limitations of tissue PD-L1 testing.

Methods: An observational cohort of patients with metastatic NSCLC treated with first-line ICI-based therapies were retrospectively assessed for a pre-planned endpoint of median and 3-year landmark overall survival (OS) based upon plasma cell-free RNA (cfRNA) PD-L1 expression by a commercial exosome-free real-time qPCR assay or tissue PD-L1 protein expression (Dako 22C3) performed in CLIA/CAP accredited laboratories.

Results: 53 contemporaneous patients in 3 patient cohorts were compared with a median follow-up 34 months. 16 patients were cfRNA plasma PD-L1 positive, including 6 (37 %) tissue PD-L1 negative or tissue quantity not sufficient for testing; 16 were plasma PD-L1 negative but tissue PD-L1 positive; 21 were both plasma and tissue PD-L1 negative. OS was identical whether positive plasma cfRNA PD-L1 expression or positive tissue PD-L1 protein expression (median OS 15 months; 3-year landmark OS 30 %; hazard ratio (HR) 0.97; 95 % CI, 0.44-2.10; p-value = 0.93). Within the positive plasma PD-L1 cohort there was no differing OS whether tissue PD-L1 positive, negative, or unknown (median OS 15 months; 3-year landmark OS 30 %; HR 1.15; 95 % CI, 0.322-4.05; p-value = 0.81). Positive plasma cfRNA expression was associated with a numerically longer median and higher 3-year OS compared to patients lacking PD-L1 expression (median 15 months versus 8 months; 3-year landmark OS 30 % versus 15 %; HR 0.57, 95 % CI 0.26-1.20; p-value = 0.11).

Conclusions: In this retrospective study of real-world metastatic NSCLC patients, plasma cfRNA PD-L1 expression was similarly predictive of ICI benefit as tissue PD-L1 protein expression.

Keywords: Immunotherapy; Liquid biopsy; NSCLC; PD-L1; Plasma cfRNA.

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Conflict of interest statement

PW is Emeritus faculty at the Brody School of Medicine at East Carolina University and a current employee of Circulogene. The other authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Overall survival comparison between positive plasma cfRNA PD-L1 patients compared to positive tissue PD-L1 protein patients.
Fig. 2
Fig. 2
Overall survival of positive plasma cfRNA PD-L1 patients whether tissue PD-L1 positive or tissue PD-L1 negative/unknown.
Fig. 3
Fig. 3
Overall survival of positive plasma cfRNA PD-L1 patients compared to patients lacking plasma/tissue PD-L1 expression.
See this image and copyright information in PMC

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