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  MA04 - Novel Approaches with IO (ID 900)

  • Event: WCLC 2018
  • Type: Mini Oral Abstract Session
  • Track: Immunooncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 13:30 - 15:00, Room 107

  • 25781

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    MA04.10 - Comprehensive Peripheral Blood Immunophenotyping and T-Cell Clonal Analysis During Neoadjuvant Immunotherapy with Atezolizumab in NSCLC (ID 13118)

    14:35 - 14:40  |  Author(s): Maciej Pietrzak
    • Abstract
    • Presentation
    • Slides

    Background
    

    Immune-checkpoint blockade targeting PD-L1/PD-1 to activate anti-tumor immunity is associated with improved response rates and survival compared to chemotherapy in selected metastatic NSCLC patients. Evaluation of the pre-therapeutic immune profile and its treatment-related evolution associated with clinical benefit will guide future immunotherapy development and support clinical decision-making. Here, we present an analysis of peripheral blood (PB) immunophenotyping and T-cell-receptor (TCR) clonality before and after immunotherapy from an ongoing 180-patient phase II study of atezolizumab as neoadjuvant therapy with stage IB-IIIB resectable NSCLC (NCT02927301; LCMC3).

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    As of February 5^th datacut, the first 54 enrolled and dosed patients are presented. The biomarker evaluable population (BEP) further subset to patients with paired PB samples analyzed within 72 hours after collection and a major pathological response (MPR) assessment. Comprehensive immune cell phenotyping (10-color flow cytometry, IMMUNOME) and TCR-Vß-analysis by flow cytometry were performed. Immunoprofile analyses were correlated with atezolizumab treatment, pathological response and PD-L1 expression.

    4c3880bb027f159e801041b1021e88e8 Result
    

    In this ongoing analysis, BEP included 31 patients. 5 patients (16%, 95% CI (5%, 34%)) had a MPR; all of which stained positive for PD-L1 by IHC using 22C3 (TPS≥1%) and SP142 (PD-L1 expression on ≥1% tumor cells (TC) and/or tumor infiltrating immune cells (IC)) at baseline. We observed significant increases in natural killer (NK) cells (p=0.005) and CD8+ T-cells (p=0.031) and a Th1-response related dendritic cell (DC) subpopulation (p=0.031) and significant decreases in B-cells (p=0.015) after treatment.

    Patients who achieved MPR show lower baseline levels of degranulated CD8+ T-cells (p=0.015), late-activated NK-cells (p=0.043), memory CD4+ (p=0.048) and memory CD8+ T-cells (p=0.032); changes in PB NK-cells (p=0.041), a decrease in M-MDSCs and a Th-2 and Th-17-response related DC subpopulation (p=0.043) in response to treatment were noted in patients with MPR versus non-MPR.

    Among the 16 patients with TC/IC 1/2/3 (> 1% PD-L1 expression) the following significant differences were observed compared to TC0/IC0 (7 patients): higher levels of late-activated CD4+ T-cells (p=0.025) and mid-activated CD8+ T-cells (p=0.044) at baseline, decrease of senescent T-cells (p=0.041), monocytic myeloid-suppressor cell subpopulations (M-MDSCs) and an increase in a Th1-response related DC subpopulation (p=0.026) after treatment.

    TCR clonality analysis showed expansions in Vß-subtypes after atezolizumab treatment.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Immunophenotyping and TCR-Vß-repertoire analysis in peripheral blood samples from NSCLC patients treated with neoadjuvant atezolizumab show differences in immune cell subsets in baseline samples and changes after treatment.

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