Author of

• 34656

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  P33 - Pathology - Immunotherapy Biomarker (ID 101)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 34664

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    P33.04 - Programmed Death-Ligand 1 (PD-L1) Changes in Non-Small-Cell Lung Cancer (NSCLC): Clinical, Pathologic, and Genomic Correlates (ID 3320)

    00:00 - 00:00  |  Presenting Author(s): Stephanie L. Alden
    • Abstract
    • Slides

    Introduction
    

    PD-L1 tumor proportion score (TPS) is imperfect in predicting response to immune checkpoint inhibitors (ICIs) in NSCLC, as PD-L1 expression can be heterogenous and dynamic. Because characteristics associated with changes in PD-L1 expression (ΔPD-L1) are poorly understood, we sought to analyze factors associated with ΔPD-L1, including mutations and copy number (CN) changes in CD274 (which encodes PD-L1). We also evaluated STK11 and KEAP1, where alterations have been associated with lower PD-L1 TPS.

    Methods
    

    We retrospectively collected clinical, pathologic, and genomic data from patients with NSCLC and at least two quantitative PD-L1 assessments. We evaluated ΔPD-L1 (second PD-L1 – first PD-L1) within each patient. When evaluating ΔPD-L1 categorically, we divided our cohort into three groups: patients with a major decrease, defined as a change from ≥50% to <50% or ≥1% to <1%; patients with a major increase, defined as a change from <1% to ≥1% or <50% to ≥50%; and patients without a major ΔPD-L1. Next generation sequencing (NGS, OncoPanel) was used to identify mutations and CN alterations. Multiple comparisons corrections used the Benjamini-Hochberg procedure, with q < 0.25 considered significant.

    Results
    

    Among 238 patients identified, 46 (19.3%) had a major decrease, 61 (25.6%) had a major increase, and 131 (55.0%) had no major ΔPD-L1 (Fig. 1A); ΔPD-L1 ranged from -90% to 95%, with a median of 0%. There was no significant difference in ΔPD-L1 as a continuous or categorical variable based on smoking status, histology, sex, genomic driver, or intervening therapy. Tissue NGS was available on both biopsies in 44 (18.5%) patients. Five cases (45.5%) with a major decrease showed acquired CN loss at CD274, whereas only two patients (8.3%) with no change and one patient (11.1%) with a major increase demonstrated acquired CD274 CN loss (Fig. 1B). Acquired CN loss in STK11 or KEAP1 was more frequent in patients with a major decrease in PD-L1, seen in approximately 30% of patients in this group, as compared to approximately 10% of patients with no change or a major increase in PD-L1 TPS. There were no acquired loss of function mutations seen in CD274, STK11, or KEAP1.

    

    Conclusion
    

    PD-L1 expression is dynamic, with few clinicopathologic correlates of ΔPD-L1. A major decrease in PD-L1 occurred in cases with acquired CD274, STK11 and KEAP1 CN loss.

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