Programmed Death Ligand 1 Heterogeneity and its Impact on Benefit from Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer.

Abstract Introduction PD-L1 expression may vary in different disease sites and at different time points of disease course. We aimed to investigate PD-L1 heterogeneity and its impact on the predictive value on immune checkpoint inhibitor (ICI) therapy in NSCLC patients. Methods PD-L1 expression was analyzed in 1,398 NSCLC patients. The predictive value of PD-L1 on ICIs in 398 patients with metastatic NSCLC was assessed. Results PD-L1 was significantly associated with biopsy sites (P = 0.004). Adrenal, liver and lymph node (LN) metastases had highest PD-L1 expression as a continuous variable and at 1% or 50% cutoff. PD-L1 expression was lower in bone and brain metastases. Among 112 patients with 2 specimens tested, 55 (49%) had major changes in PD-L1 falling into different clinically relevant categories ( Conclusion PD-L1 varies substantially across different anatomic sites and changes during clinical course. PD-L1 from different biopsy sites may have different predictive value for benefit from ICIs in NSCLC.