Author of

• 18502

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  P3.02c - Poster Session with Presenters Present (ID 472)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18574

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    P3.02c-072 - Predictive Immunologic Markers of Response to Nivolumab in Non-Small Cell Lung Cancer (ID 6228)

    14:30 - 14:30  |  Author(s): P. Carrega
    • Abstract

    Background:
    Nivolumab has become a consolidated therapeutic approach for previously treated non-small cell lung cancer (NSCLC); however, consistent prognostic and predictive factors are still lacking. Since these agents act by enhancing the immune response against tumor cells, it is possible that distinctive patterns in the circulating T cell sub-populations might be associated with different responsiveness. The aim of this study is to determine whether variations in these sub-populations might predict objective response to nivolumab in NSCLC.
    
    Methods:
    Blood samples were collected and stored from patients receiving nivolumab (3 mg/Kg every 14 days) for advanced NSCLC within a single-institutional translational research study conducted in the San Martino Hospital – National Institute for Cancer Research, Genova, Italy (approved by the local ethical committee). Sample collection was performed before each administration for 4 consecutive cycles, followed by computed tomography (CT)-scan. Response assessment was performed with the response evaluation criteria in solid tumors (RECIST) v. 1.1 and the immune-related response criteria (irRC); responses were defined as partial response (PR), stable disease (SD), and progressive disease (PD). Additional CT-scans were performed at 4 cycles intervals. Peripheral blood mononuclear cells (PBMC) were analyzed for the frequency of the major adaptive cell subsets, including B cells, natural killer (NK) cells, and T-cells; the latter were divided into CD8+ T cells, exhausted CD8+ T cells, CD4+ cells, and regulatory T cells (Tregs); the relative frequencies and the ratios between the sub-populations at each sample collection were compared with radiological response.
    
    Results:
    Fifty-four patients were considered eligible: median age= 70 (44-85); male/female: 70%/30%; current or former smokers= 87%; non-squamous/squamous histology= 80%/20%. Patients achieving PR at the first RECIST assessment had a significant upregulation of Tregs (CD4+ Foxp3+ CD39+ cells; p= 0.021), as well as a decreased CD8+/Treg ratio (p= 0.033) at the baseline sample. Conversely, patients experiencing PD at the first RECIST assessment had a significantly upregulated CD8+/Treg ratio at cycle 2 (p= 0.029). Finally, patients experiencing PD at irRC had a higher proportion of activated T cells (PD1+ CD56+ CD3+) compared to the other patients (P= 0.018) at cycle 2.
    
    Conclusion:
    The proportions of Tregs and activated T cells appear to be correlated with different responses to nivolumab according to RECIST and irRC. While the immunologic mechanism at the basis of these findings has to be defined, further studies involving PBMC as predictors of response to immunotherapy for NSCLC are highly advised.