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Luigi Pirtoli



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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • 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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      P2.01-21 - Antigen Cascade Triggering Correlates with Prolonged Survival in Advanced NSCLC Patients Undergone PD-1 Blockade with Nivolumab. (ID 13724)

      16:45 - 18:00  |  Author(s): Luigi Pirtoli

      • Abstract
      • Slides

      Background

      Programmed-cell-death receptor-1 (PD-1) blockade by Nivolumab mAb is a promising treatment for metastatic (m) NSCLC patients, which may yield dramatic improvement in benefit and survival. It acts by rescuing the antitumor activity of PD-1-inactivated tumor-infiltrating-lymphocytes, residual of a pre-existing immune-reaction naturally occurring or consequential to prior radio/chemo-therapy. T-cell rescue is indispensable for the immediate response to the treatment, however, in order to obtain a prolonged effect on patients’ survival continuous immune-priming able to supply fresh immune-effectors with antitumor activity, appears to be indispensable. We have thus investigated, whether Nivolumab treatment is also able to promote antigen cascade and cross-priming measured as occurrence of auto-antibody and auto-immunity and whether these effects are predictive of positive outcome in mNSCLC patients

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a multi-institutional retrospective study including ninety-eight mNSCLC patients who received Nivolumab therapy (3mg/kg every 15 days) between September 2015 and March 2018. These patients had received at least a previous line of platinum-based doublet +/- bevacizumab. Log-rank test and Mantel-Cox analysis were carried-out to correlate patients’ PFS and OS with different parameters including baseline and post-treatment levels of inflammatory markers (CPR, ESR, LDH); ANA, ENA, ASMA auto-antibodies (AAbs); hormone-profiling; Th1, Th2, Th17 cytokines; regulatory-T-cells, different CTL subsets, and natural killers.

      4c3880bb027f159e801041b1021e88e8 Result

      We recorded a PFS and OS of 12.5 [95%CI:9.9-15.0] and 15.3 [95%CI:12.8-17.9] months, respectively, not correlated to histology, number of previous chemotherapy lines, radiotherapy, or TKI use. A better outcome was found in males (OS, HR=2.3, 95%CI: 1.1-4.8, P=0.028), in those who presented autoimmunity signs (PFS: 17.2 vs. 6.7 months; HR=0.30, 95% CI: 0.15-0.57, p<0.001; OS:20.8 vs. 9.7 days; HR=0.24, 95% CI: 0.11-0.50, p<0.001) and those who showed early rise (within thirty days) of one (score 1, HR=0.235, 95% CI: 0.084-0.654. P=0.018) or more AAbs (score 2 HR= 0.22, 95% CI: 0.081-0.624, P= 0.001). Finally, Cox analysis revealed a predictive role for treatment-related early increase in eosinophil cell counts (OS, HR: 0.68, 95% CI: 0.57-0.81, P=0.031).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Antigen cascade triggering measured as early occurrence of ANA ENA, ASMA AABs and subsequently, self-limiting autoimmunity is strongly predictive of longer survival in mNSCLC patients receiving treatment with Nivolumab. Additionally, the occurrence of AAbs strongly supports the occurrence of Nivolumab- dependent antigen cascade and cross-priming. These results offers a strong rationale to design future perspective trials in NSCLC patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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