Use of the 22C3 anti–programmed death‐ligand 1 antibody to determine programmed death‐ligand 1 expression in cytology samples obtained from non–small cell lung cancer patients

BACKGROUND: Pembrolizumab monotherapy is a standard-of-care treatment for the first- and second-line treatment of advanced non-small cell lung cancer with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) values ≥ 50% and ≥ 1%, respectively. PD-L1 testing with the PD-L1 immunohistochemistry (IHC) 22C3 pharmDx companion assay has been validated on tumor tissue with the Dako Autostainer Link 48 (ASL48). 22C3 anti-PD-L1 antibody-based laboratory-developed tests (LDTs) compatible with other autostainers and cytology samples are essential to support pembrolizumab treatment decisions across institutions globally. METHODS: ASL48 and BenchMark Ultra LDTs were optimized for the evaluation of cytology samples through comparisons with cell lines with known PD-L1 expression levels (strong, moderate, and negative). The PD-L1 TPS was then evaluated for 70 paired biopsy and cytology samples (bronchial washes, n = 40; pleural effusions, n = 30) with these LDTs. Biopsy and cytology LDT TPS values were also compared with a subset of biopsy samples (n = 37) evaluated with the PD-L1 IHC 22C3 pharmDx assay on the ASL48. RESULTS: Intraclass correlation coefficients of 0.884 to 0.898 were observed for biopsy samples versus cytology samples with the ASL48 and BenchMark Ultra LDTs. Concordance was high, regardless of the TPS cut point (<1% vs ≥ 1% and <50% vs ≥ 50%), sample type (pleural effusion vs bronchial wash), or tumor histology (adenocarcinoma vs squamous cell carcinoma). Concordance was high for each LDT versus the PD-L1 IHC 22C3 pharmDx assay. CONCLUSIONS: ASL48 and BenchMark Ultra 22C3 antibody concentrate-based LDTs have been validated for PD-L1 testing in cytology samples, and they will support reliable, high-quality PD-L1 testing across regions globally. Cancer Cytopathol 2018;126:264-74. © 2018 American Cancer Society.