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Youjin Kim



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    OA14 - Update of Phase 3 Trials and the Role of HPD (ID 148)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
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      OA14.07 - Clinical and Genetic Characterization of Hyperprogression Based on Volumetry in Advanced NSCLC Treated with Immunotherapy (Now Available) (ID 1067)

      11:30 - 13:00  |  Presenting Author(s): Youjin Kim

      • Abstract
      • Presentation
      • Slides

      Background

      Hyperprogressive disease (HPD), characterized by accelerated tumor progression, has been proposed as a new pattern of progression following immune checkpoint inhibitor (ICI) treatment. The aim of this study was to describe the characteristics of HPD and investigate its predictive markers.

      Method

      Clinical and radiological findings of 335 advanced non-small cell lung cancer (NSCLC) patients treated with ICI monotherapy were retrospectively analyzed. Radiological data were quantitatively and longitudinally analyzed for tumor size and volume by comparing baseline and follow-up computerized tomography results. The findings were matched to individual genomic profiles generated by deep sequencing of 380 genes.

      Result

      Among 135 patients with progressive disease (PD), as assessed by RECIST, 48 (14·3% of total and 35·6% among PD) and 44 (13·1% of total and 32·6% among PD) were found to have HPD by volumetric (HPDV) and one-dimensional (HPDR) analysis, respectively. HPDV patients were associated with significantly inferior overall survival (OS) compared with non-HPDV PD patients (median OS (months), 4·7 [95% confidence interval (CI), 3·5–11·9)] vs. 7·9 [95% CI, 6·0–13·5], p=0·004); OS did not differ between HPDR and non-HPDR patients. HPDV status was an independent OS factor. Derived neutrophil-to-lymphocyte ratio (dNLR) greater than 4 and lactate dehydrogenase (LDH) greater than the upper normal limit were significantly associated with HPDV. Moreover, we identified coinciding KRAS and STK11 mutations in the HPDV cohort (3/16), while none were found in the non-HPDV cohort (0/28).

      Conclusion

      Defining HPD treated with ICI based on volumetric measurement is more precise than that based on one-dimensional analysis. Pre-ICI dNLR, LDH, and concurrence of STK11 and KRAS mutations could, thus, be used as potential biomarkers for HPD prediction.

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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.04-24 - Circulating Suppressive Immune Cells Predict the Efficacy of Anti PD-1 Immunotherapy in Patients with Advanced Non-Small Cell Lung Cancer (ID 466)

      09:45 - 18:00  |  Author(s): Youjin Kim

      • Abstract

      Background

      The major suppressive immune cells in tumor sites are myeloid derived suppressor cell (MDSC), tumor associated macrophage (TAM), and regulatory T (Treg) cell, and the major roles of these suppressive immune cells include hindering T cell activities and supporting tumor progression and survival. In this study, we analyzed the pattern of various circulating suppressive immune cells in patients with non-small cell lung cancer (NSCLC) to see whether those suppressive immune cells hinder T cell activities leading to poor clinical outcomes.

      Method

      Baseline blood samples were collected from stage I to IV NSCLC patients (n=59), and baseline and one week after the therapy paired blood samples from stage IIIB to IV NSCLC patients (n=83) undergoing anti PD-1 immunotherapy either pembrolizumab or nivolumab. The efficacies of peripheral blood suppressive immune cells along with CD39+CD8+ T cells individually or collectively in anti-PD-1 immunotherapy were evaluated using flow cytometry and T cell suppressive assay.

      Result

      G-MDSCs, M-MDSCs, TAMs, Treg cells, and CD39+CD8+ T cells increased according to NSCLC stage, and MDSCs effectively suppressed T cell activities and induced T cell exhaustion ex vivo. Further, the analysis of 83 NSCLC patients treated with anti-PD-1 immunotherapy demonstrated that low G-MDSCs (PPFS = 0.03, Pos = 0.04), M-MDSCs (PPFS = 0.04, Pos = 0.005), TAMs (PPFS = 0.007, Pos = 0.01), and CD39+CD8+ T cells (PPFS = 0.57, Pos = 0.02) were associated with longer progression-free survival (PFS) and overall survival (OS) compared with high groups. When we performed combined analysis of three suppressive immune cells, G-MDSCs, M-MDSCs, and TAMs collectively, patients who had low frequency of all three suppressive immune cells showed more prominent difference of PFS (6.7 months vs 2 months; P = 0.006), OS (8.5 months vs 4.2 months; P = 0.004), and response rate (94.5% vs 50%) compared to patients with high levels of all three suppressive immune cells. We further sorted patients with all suppressive immune cells plus CD39+CD8+ T cells low and high. Again, PFS (6.1 months vs 0.8 months; P = 0.006), OS (11 months vs 2.4 months; P = 0.01), and response rate (85.7% vs 16.7%) of all suppressive immune cells low and CD39+ CD8+ T cells low group were significantly increased.

      Conclusion

      The analysis of 83 advanced NSCLC patients treated with anti-PD-1 immunotherapy demonstrated that G-MDSC, M-MDSC, TAM and CD39+CD8+ T cell frequencies in peripheral blood individually and collectively might be useful as potential predictive biomarkers.