Author of

• 35377

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  P14 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) - Immuno-Biology (ID 153)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 35411

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    P14.21 - Baseline Derived Neutrophil-to-Lymphocyte Ratio (dNLR) and Clinical Outcomes to First-Line Pembrolizumab in NSCLC with High PD-L1 (≥50%)  (ID 3725)

    00:00 - 00:00  |  Presenting Author(s): Joao Victor M. Alessi
    • Abstract
    • Slides

    Introduction
    

    An elevated peripheral blood neutrophil-to-lymphocyte ratio (NLR) is a negative prognostic marker for patients with non-small cell lung cancer (NSCLC) receiving second-line immune checkpoint inhibitors. We sought to determine if NLR is also associated with clinical outcomes to first-line pembrolizumab among patients with NSCLC and a PD-L1 tumor proportion score (TPS) of ≥50%.

    Methods
    

    We retrospectively analyzed the derived NLR (dNLR, defined as absolute neutrophils / [leukocytes – neutrophils]) prior to initiation of first-line pembrolizumab in patients with metastatic NSCLC with a PD-L1 TPS ≥50% and lacking genomic alterations in EGFR and ALK. Patients receiving systemic glucocorticoids or other immunosuppressive therapies were excluded from the analysis. A receiver operating characteristic (ROC) curve was used to investigate a dNLR threshold to discriminate for objective response rate (ORR).

    Results
    

    Among 145 patients with NSCLC treated with first-line pembrolizumab, the ORR was 42.1% (95%CI: 34.9-49.4%). At a median follow-up of 24.7 months (95%CI: 23.6-25.9), the median progression-free survival (mPFS) was 7.5 months (95%CI: 5.5-11.1), and the median overall survival (mOS) was 28 months (21.0-NR). In 85% of cases (N=123), the complete blood count used for analysis was collected on the same day prior to the first dose of pembrolizumab. ROC analysis identified an optimal grouping dNLR cut-off of 2.6. The majority of patients (57.2%, N=83) had a dNLR ≤2.6, and 42.8% (N=62) had a dNLR >2.6. Baseline clinicopathological characteristics were balanced between the dNLR ≤2.6 vs >2.6 groups in terms of age, performance status, tobacco use, histology, KRAS mutation status, presence of other potentially targetable driver mutations (BRAF, MET, HER2, RET), albumin level, tumor mutation burden (TMB), and PD-L1 distribution (50-89% vs ≥90%). Compared to patients with a dNLR >2.6, patients with dNLR ≤2.6 had a significantly higher objective response rate (ORR 53% versus 27.4%, P=0.002), a significantly longer median progression-free survival (mPFS 11.2 months versus 3.7 months, HR: 0.50 [95% CI: 0.34-0.74], P<0.0001), and a significantly longer median overall survival (mOS not reached versus 14.6 months, HR: 0.32 [95% CI: 0.19-0.53], P<0.001). After adjusting for performance status, PD-L1 distribution, and TMB level, dNLR ≤2.6 was significantly associated with improved mPFS (HR: 0.53 [95% CI: 0.33-0.85], P=0.008) and mOS (HR: 0.30 [95% CI: 0.16-0.56], P<0.001).

    Conclusion
    

    Among patients with NSCLC and a PD-L1 TPS ≥50%, a dNLR >2.6 is associated with unfavorable clinical outcomes. Clinical trials exploring first-line immunotherapy combinations should consider stratifying by dNLR to ensure that randomized groups are evenly balanced for this negative prognostic marker.

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