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Matthew Rosenbaum

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    P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.04-21 - The Utility of PD-L1/CD8 Dual Immunohistochemistry for Prediction of Response to Immunotherapy in Non-Small Cell Lung Cancer (NSCLC) (ID 13815)

      16:45 - 18:00  |  Author(s): Matthew Rosenbaum

      • Abstract


      PD-L1 immunohistochemistry (IHC) is an important predictive biomarker for PD-(L)1 blockade in advanced non-small cell lung cancer (NSCLC); however, this assay is imperfect. The presence of CD8+ tumor infiltrating lymphocytes (TILs) may be a complimentary biomarker for response to immunotherapy. Thus, we examined the performance of PD-L1/CD8 dual IHC (dIHC) in two cohorts of NSCLC patients receiving immunotherapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients were identified through retrospective review of medical oncology and pathology databases. The first cohort predominantly received nivolumab as a 2nd or later line treatment; tissue samples were mainly obtained at initial diagnosis. The second cohort received pembrolizumab as a first line therapy, and tissue samples were procured immediately before the initiation of immunotherapy. PD-L1/CD8 dIHC was performed on those tissue samples. Percentage of tumor cells with membranous PD-L1 expression and CD8+ stromal cells were measured, and CD8+ TILs were semi-quantitatively evaluated. The quantities of CD8+ T cells were dichotomized with appropriate cut-offs.

      4c3880bb027f159e801041b1021e88e8 Result

      Eighty-four patients were identified, including 60 in the Nivolumab cohort (NC) and 24 in the Pembrolizumab cohort (PC). In the NC, PD-L1 expression ≥1% was marginally associated with improved progression-free survival (PFS, p=0.09), and an increased rate of response (p=0.08). CD8+ TILs and stromal cells did not correlate with outcome. However, a subset of PD-L1-positive patients who showed abundant CD8+ TILs and stromal cells had significantly reduced PFS (p=0.04). In the PC cohort, all cases chosen exhibited PD-L1 expression in ≥50% of tumor cells. Increased CD8+ TILs were correlated with improved PFS, (p=0.0194), and an increase in both CD8+ TILs and stromal cells was also associated with improved PFS (p= 0.0238).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Although limited by small sample size, this study suggests that PD-L1/CD8 dIHC improves the prediction of response to the PD-1/PD-L1 blockade in advanced NSCLC patients when it is performed on tissue samples obtained immediately before the initiation of the blockade as first-line therapy . However, for the 2nd or later line of treatment, dIHC on archival tissue samples obtained before initial therapy provides a useful but less clear picture of the tumor immune microenvironment. Reduced PFS seen in patients with PD-L1 expression and abundant CD8+ TILs and stromal cells may be due to T-cell exhaustion after the chemotherapy before the PD-1/PD-L1 blockade. These findings suggest that PD-L1/CD8 dIHC may be useful for treatment response stratification in advanced lung cancer patients.