Author of

• 30943

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  P2.04 - Immuno-oncology (ID 167)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Immuno-oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 30976

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    P2.04-31 - Immune Phenotypic Biomarkers in Locally Advanced Non-Small Cell Lung Cancer Treated with Definitive Chemoradiation and Atezolizumab (ID 2597)

    10:15 - 18:15  |  Author(s): Hui Gao
    • Abstract

    Background
    

    Consolidation durvalumab is the current standard of care for locally advanced non-small cell lung cancer (LA-NSCLC) after chemoradiation (CRT). However, predictive and prognostic biomarkers of response to immunotherapy are still poorly characterized. In particular, minimally-invasive blood-based biomarkers that can be sequentially assessed during therapy may prove useful in understanding the characteristics of response and optimal sequencing of therapy. We report serial blood immune-phenotyping of patients undergoing concurrent chemoradiation therapy (CRT) with PD-L1 blockade with atezolizumab.

    Method
    

    Between February 2016 and October 2018, 40 LA-NSCLC patients were evaluated in conjunction with the single-institution DETERRED trial. The first 10 patients were treated with carboplatin/paclitaxel chemotherapy and atezolizumab for two cycles followed by maintenance atezolizumab for 1 year after completing CRT, followed by 30 patients treated with atezolizumab concurrent with CRT followed by chemotherapy/atezolizumab and maintenance atezolizumab. In all, 38 patients were evaluable. Peripheral blood was drawn at the beginning (baseline), midway through CRT (2-4 weeks), and at the end of CRT, with periodic follow up samples for up to two and a half years. Immune phenotyping was performed by flow cytometry on fresh, whole blood within 24 hours of phlebotomy. Cox regression was preformed to assess biomarker correlations with survival.

    Result
    

    At the second blood sample midway through CRT, patients who eventually progressed had a larger increase from baseline in the percentage of peripheral blood CD4 T helper cells expressing PD-1 (p = 0.042) and this change was associated with both progression-free (PFS, p = 0.039) and overall survival (OS, p = 0.042). Progressors had a mean increase of 2.5 percentage points while non-progressors had a mean drop of 1.9. At the first post-CRT follow-up, an increase in the percentage of CD8 cytotoxic T lymphocytes expressing PD-1 was negatively associated with survival (PFS p = 0.0015, OS p = 0.023) as well as the percentage of granulocytic myeloid suppressor cells (PFS p = 0.0089, OS p = 0.034). These comparisons were not significant when corrected for multiple testing. However, the change in CD4 PD1 after 2-4 weeks of CRT was an independent prognostic indicator of PFS in multivariate cox regression analysis including age, stage, and histology (p = 0.02, hazard ratio 1.2, 95% CI 1.03 to 1.4).

    Conclusion
    

    Increases in peripheral blood lymphocytes expressing PD1 and myeloid suppressor cells may be prognostic for locally advanced patients treated with CRT and immune checkpoint blockade but additional studies are needed to verify these markers in immunotherapy resistance.