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Sylvie Labrune

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    MA10 - Considerations in Immunotherapy / Real World (ID 911)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 105
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      MA10.03 - Plasmatic Evaluation of the Intestinal Barrier and Blood Microbiota, and Antibiotic Use in Non-Small Cell Lung Cancer Patients Treated with Nivolumab (ID 13863)

      10:40 - 10:45  |  Author(s): Sylvie Labrune

      • Abstract
      • Presentation
      • Slides


      Recent data suggest that gut microbiota and antibiotic use affect the efficacy of immune checkpoint inhibitors. We aimed to evaluate the predictive role of blood microbiota, plasma citrulline (marker of the intestinal barrier), and the impact of early (from 2 months before until 1 month after beginning of nivolumab) and late (after 1 month of nivolumab) antibiotic use on nivolumab efficacy in NSCLC patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We included consecutive patients with advanced NSCLC treated with nivolumab between July 2014 and December 2017. Plasma tests were taken prospectively during treatment. The microbial population present in the plasma samples was determined using sequencing of variable regions of the 16S rRNA bacterial gene at M0. Plasma citrulline concentrations were evaluated by ion exchange chromatography at month (M) 0, M2, M4 and M6 of nivolumab.

      4c3880bb027f159e801041b1021e88e8 Result

      Seventy-two patients were included (male: 62%; smokers: 87%; adenocarcinoma: 63%). Early use of antibiotics (EUA) (n=28/72) was associated with poor overall survival (OS) (median 5.1 months, versus 13.4 months without EUA, p=0.03), whereas later use of antibiotic during treatment had no significant effect. Thirty-six patients (50%) had serial plasma samples available for analyses. The composition of blood microbiota at M0 was associated with tumor response and long-term benefit of nivolumab, with a significant impact of Paludibacilum, Gemmatimonadaceae and Nocardioides. Patients with long-term benefit of nivolumab had significantly higher plasma citrulline concentrations than other patients, at M0, M2 and M4, and maintained high citrulline concentrations at M6. Median progression-free survival (PFS) and OS for patients with citrulline ≥20µM at M0 were 7.9 months and not reached, versus 1.6 months (p<0.0001) and 2.2 months (p<0.0001) for patients with citrulline <20µM, respectively. Patients with EUA had lower median citrulline concentrations at M0 (17µM [IQR 15-30] versus 31µM [IQR 21.3-40.5]; p=0.06).

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study confirms the negative impact of EUA during nivolumab treatment, and suggests that plasma evaluation of the intestinal barrier and blood microbiota may help to predict the outcome of NSCLC patients treated with nivolumab.


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