PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of Blueprint phase 2 project.

The Blueprint (BP) PD-L1 immunohistochemistry (IHC) comparability project is a pivotal academic/professional society and industrial collaboration to assess the feasibility of harmonizing the clinical use of five independently developed commercial PD-L1 IHC assays. The goals of BP phase 2 (BP2) were to validate the results obtained in BP1, using real world clinical lung cancer samples (n=81) of various histological and sample types, with all five trial-validated PD-L1 assays (22C3, 28-8, SP142, SP263, and 73-10), by an international panel of pathologists. BP2 also assessed the reliability of PD-L1 scoring by digital images, and on samples prepared for cytology examination. PD-L1 expression was assessed for percentage (tumor proportional scoring or TPS) tumor cells (TC) and immune cell (IC) areas showing PD-L1 staining, with TC scored continuously or categorically with cut-offs used in checkpoint inhibitor trials. The results showed highly comparable staining by 22C3, 28-8 and SP263 assays, less sensitivity with SP142 assay, and higher sensitivity with 73-10 assay to detect PD-L1 expression on TC. Glass slide and digital image scorings were highly concordant (Pearson correlation >0.96). There was very strong reliability among pathologists in TC PD-L1 scoring with all assays (overall intraclass correlation coefficient/ICC 0.86-0.93), poor reliability in IC PD-L1 scoring (overall ICC 0.18-0.19), and good agreement in assessing PD-L1 status on cytology cell blocks materials (ICC 0.78-0.85). BP2 consolidates the analytical evidence for interchangeability of 22C3, 28-8, and SP263 assays and lower sensitivity of SP142 assay for scoring TPS on TC, and demonstrates greater sensitivity of 73-10 compared to other assays.