Abstract
Targeting of the programmed cell death protein (PD-1)/programmed death-ligand 1 (PD-L1) axis with checkpoint inhibitors has changed clinical practice in non-small cell lung cancer (NSCLC). However, clinical assessment remains complex and ambiguous. We aim to assess whether digital image analysis (DIA) and multiplex immunofluorescence can improve the accuracy of PD-L1 diagnostic testing. A clinical cohort of routine NSCLC patients reflex tested for PD-L1 (SP263) immunohistochemistry (IHC), was assessed using DIA. Samples of varying assessment difficulty were assessed by multiplex immunofluorescence. Sensitivity, specificity, and concordance was evaluated between manual diagnostic evaluation and DIA for chromogenic and multiplex IHC. PD-L1 expression by DIA showed significant concordance (R² = 0.8248) to manual assessment. Sensitivity and specificity was 86.8% and 91.4%, respectively. Evaluation of DIA scores revealed 96.8% concordance to manual assessment. Multiplexing enabled PD-L1+/CD68+ macrophages to be readily identified within PD-L1+/cytokeratin+ or PD-L1-/cytokeratin+ tumor nests. Assessment of multiplex vs. chromogenic IHC had a sensitivity and specificity of 97.8% and 91.8%, respectively. Deployment of DIA for PD-L1 diagnostic assessment is an accurate process of case triage. Multiplex immunofluorescence provided higher confidence in PD-L1 assessment and could be offered for challenging cases by centers with appropriate expertise and specialist equipment.
Highlights
Durable tumor regression and prolonged stabilization of disease in patients treated with immune checkpoint blockade therapy has changed the paradigm with cancer immunotherapy
We demonstrate the concordance with manual pathological assessment, evaluate the potential for digital image analysis (DIA) utilization in routine clinical diagnostics, the reasons for clinical discordance, and recommendations for programmed death-ligand 1 (PD-L1) case triage
There were 703 cases submitted for PD-L1 analysis and had clinical reports issued
Summary
Durable tumor regression and prolonged stabilization of disease in patients treated with immune checkpoint blockade therapy has changed the paradigm with cancer immunotherapy. The expression of programmed death-ligand 1 (PD-L1) has been associated with profound responses to anti– programmed cell death protein (PD-1) therapy and led to several U.S Food and Drug Administration approved PD-L1 diagnostic assays for melanoma, non–small cell lung cancer (NSCLC), and gastric, bladder, and cervical cancers [1,2,3,4]. We recently reported on the routine challenges faced clinically in assessment of PD-L1 [5]. This is in addition to the myriad of companion diagnostic assays available for PD-L1 and the variation in assessment criteria across tumor types [6,7,8].
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