Plasma Cell-Free RNA PD-L1 Expression and Clinical Outcomes With Immunotherapy

Abstract

<h3>Purpose/Objective(s)</h3> Programmed death ligand-1 (PD-L1) expression is predictive of immunotherapy benefit. However, tissue PD-L1 protein immunohistochemical testing can be fraught with tissue acquisition and heterogeneity limitations. PD-L1 expression by RNA sequencing can be performed by both tissue and plasma with tissue PD-L1 protein correlations. What has not been well characterized is the correlation of plasma cfRNA PD-L1 and clinical outcomes with immunotherapy. Plasma cfRNA PD-L1 expression was evaluated and correlated with immunotherapy benefit in advanced non-small cell lung cancers (NSCLC). <h3>Materials/Methods</h3> Patients with advanced NSCLC undergoing plasma next-generation sequencing including plasma cfRNA PD-L1 testing in a CLIA and CAP accredited laboratory were retrospectively identified and evaluated at a single institution. Plasma PD-L1 positive patients underwent a de-identified chart abstraction to identify those patients with advanced NSCLC treated with front line immunotherapy regimens and those who received cytotoxic chemotherapy alone. <h3>Results</h3> 16 patients with plasma PD-L1 expression treated with front line immunotherapy regimens including single-agent immune checkpoint inhibitors and combinatorial chemo-immune or chemo-immune-bevacizumab regimens, were assessed for overall survival (OS). 11 patients with plasma PD-L1 expression who received chemotherapy alone were identified and evaluated as a non-immunotherapy OS comparison. Median OS for the immunotherapy treated patients was 13 months with a 30% 3-year landmark OS versus 4 months median OS and a 10% 3-year landmark OS for those treated with chemotherapy alone. Comparative log-rank test p-value 0.0091 and a hazard ratio of 0.36 (95%-CI 0.13-0.99). <h3>Conclusion</h3> Plasma cfRNA PD-L1 expression is predictive of a statistically significant survival benefit from immunotherapy treatment compared to chemotherapy in the first line treatment of advanced NSCLC. The 3-year landmark OS of 30% parallels tissue PD-L1 directed immunotherapy-based treatment outcomes. The clinical utility of plasma cfRNA PD-L1 to overcome tissue acquisition and PD-L1 protein heterogeneity limitations and to study the dynamic nature of PD-L1 expression with non-immune cancer treatments and potential immunotherapy response monitoring are undergoing ongoing research.