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Alessandro Perez



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    P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.04-10 - Early Monitoring of Blood Biomarkers to Predict Nivolumab Efficacy in NSCLC Patients  (ID 14101)

      16:45 - 18:00  |  Author(s): Alessandro Perez

      • Abstract
      • Slides

      Background

      In the present study we investigated whether early dynamic changes of circulating free (cf) DNA levels as well as peripheral blood cells count could predict resistance to nivolumab in pre-treated patients with advanced non-small cell lung cancer (NSCLC).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From September 2015 to January 2018, 45 NSCLC patients receiving i.v nivolumab 3 mg/kg every two weeks were included within a translational study. All the patients underwent CT-scan every 6 cycles and responses were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Peripheral blood samples were obtained from the patients at baseline and at fourth cycle of therapy. The quantification of cfDNA (ng/µL plasma) was performed by qubit dsDNA HS assay and confirmed by qPCR evaluating a 115 bp fragment of ALU repeat. The median cfDNA level as well as the median neutrophil to lymphocyte ratio (NLR) value were calculated at the first and the fourth infusion of nivolumab. Time to progression (TTP) and overall survival (OS) were determined.

      4c3880bb027f159e801041b1021e88e8 Result

      Elevated baseline cfDNA level was associated with inferior OS (7.2 vs 13.5 months, p=0.04) while high pre-treatment NLR predicted inferior TTP (4.5 vs 9.7 months, p=0.006). Patients with increased median cfDNA level >20% at fourth cycle reported significantly worse OS and TTP (OS: 5.7 vs 14.2 months, p<0.001; TTP: 3.3 vs 10.2 months, p<0.001). Patients with increased median NLR >20% at fourth cycle of therapy showed significantly worse OS and TTP (OS: 8.7 vs 14.6 months, p=0.035; TTP: 5.2 vs 10.3 months, p=0.039). Patients with a simultaneous increase >20% of both cfDNA level and NLR value showed significant worse survival outcomes as compared to patients with only one increased parameter or not increase of both parameters (OS: 5.8 vs 11.1 vs 11.5 vs 15.4 months, p=0.012; TTP: 3.2 vs 6.5 vs 7.33 vs 11.9, p= 0.028).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Early increase of both cfDNA level and NLR value is a marker of resistance to nivolumab and predict worse survival outcomes in pre-treated patients with advanced NSCLC, suggesting a potential role in the real time monitoring of immunotherapy efficacy.

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