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A. Poot



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    MA 05 - Immuno-Oncology: Novel Biomarker Candidates (ID 658)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      MA 05.07 - Whole Body PD-1 and PD-L1 PET in Pts with NSCLC (ID 9219)

      15:45 - 17:30  |  Author(s): A. Poot

      • Abstract
      • Presentation
      • Slides

      Background:
      Tumor PD-L1 IHC relates moderately with treatment outcome following anti-PD1 therapy in pts with NSCLC and single biopsies do not account for tumor heterogeneity. Aim: 1. Assess safety of the PET procedures. 2. Quantify [89]Zirconium-labeled nivolumab ([89]Zr-nivo) and [18]F-labeled BMS-986192 ([18]F-PD-L1) uptake. 3. Assess tracer uptake heterogeneity. 4. Correlate tracer uptake with PD-1/PD-L1 IHC in tumor, stroma and with treatment outcome.

      Method:
      NSCLC pts eligible for treatment with nivolumab were included. Pts received whole body [18]F-PD-L1 and [89]Zr-nivo PET scans. Baseline tumor biopsy was required to assess PD-(L)1 IHC status (28.8 assay). SUV~peak~ was calculated for delineable lesions and correlated to PD-(L)1 IHC and response after 12 wks of nivolumab treatment.

      Result:
      10 pts (3 ≥50%, 5 ≥1%, 5 negative by PD-L1 IHC) were enrolled and 37 lesions analysed. No toxicity related to radiotracer was observed. Tumor uptake of both tracers was visualized in all pts, but not in all lesions. Tracer uptake varied among pts with mean [18]F-PD-L1 SUV~peak~ 4.6, range 0.5 - 14.4 and mean [89]Zr-nivo SUV~peak~ 5.0, range 1.6 – 11 (p=0.03) and within pts with mean SUV~peak~ difference 3.6-fold (±2.1) and 2.4-fold (±0.77) between lesions for [18]F-PD-L1 and [89]Zr-nivo, respectively. For lesions with ≥50% PD-L1 IHC, mean [18]F-PD-L1 SUV~peak~ was 8.0 (±4.7) as compared to 3.5 (±1.6) for lesions with <50% PD-L1 IHC (p=0.03). For tumors with high TIL/ stromal PD-1 expression, mean [89]Zr-nivo SUV~peak~ was 8.6 (±2.4) as compared to 6.1 (±2.1) for lesions with low PD-1 expression (p=0.1). Mean SUV~peak ~for [18]F-PD-L1 was 8.4 (±5.4) for pts with PR and 4.5 (±2.9) for pts with PD/SD (p=0.3). Mean SUV~peak~ for [89]Zr-nivo was 7.8 (±1.8) for pts with PR and 5.4 (±2.2) for pts with PD/SD (p=0.2).

      Conclusion:
      1. PET-imaging with both tracers is safe and feasible, with good tumor-to-normal tissue contrast. 2. Tumor uptake showed heterogeneity among pts and among tumors within pts. 3. Pts with ≥50% tumor PD-L1 expression showed higher [18]F-PD-L1 uptake. 4. Pts with high PD-1 expression showed higher [89]Zr-nivo uptake, and pts with PR demonstrated higher [18]F-PD-L1 and [89]Zr-nivo tracer uptake than pts with PD/SD, although these are without statistical significance which may be due to the small dataset.

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