Author of

• 20171

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  P2.07 - Immunology and Immunotherapy (ID 708)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Immunology and Immunotherapy
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23397

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    P2.07-022 - Inflammatory Cytokine Induction after Anti-PD-1 Ab Administration Relates to the Efficacy and Safety in Patients with Non-Small Cell Lung Cancer (ID 8636)

    09:30 - 16:00  |  Presenting Author(s): Yuichi Ozawa
    • Abstract

    Background:
    PD-1/PD-L1 interaction affects various immune cells, including macrophage and dendritic cells, which play crucial roles in anti-cancer immunity. Early alteration of inflammatory cytokines, such as IL-6, TNF-α, or CRP, which is a surrogate marker for IL-6, following anti-PD-1 antibody administration may represent activation of those cells and be related to the efficacy and safety of anti-PD-1 antibody treatment; however, these remain unexplored thus far.
    
    Method:
    Serum IL-6 and TNF-α were measured with CLEIA/ELISA method in 10 non-small cell lung cancer patients having evaluable serums before and after anti-PD-1 antibody (nivolumab or pembrolizumab) administration. For CRP, medical records were reviewed and serum CRP was measured in 34 non-small cell lung cancer patients before and after anti-PD-1 antibody administration. The relationship of IL-6, TNF-α, and CRP alterations within 7 days with the response rate and frequency of severe adverse events (≥ Grade 3) (SAEs) was analyzed.
    
    Result:
    In 10 patients analyzed for IL-6/TNF-α, age was 68 (45 – 74) (median [range]) years, PS 0/1: 7/3, Sqc/Non-Sqc: 4/6, and the days before/after anti-PD-1 antibody administration were 0 (0 – 7)/ 3.5 (2 – 7). IL-6/TNF-α was 20.3 (2.6 – 49.9) pg/mL /1.6 (0.7 – 6.3) pg/mL at pre-treatment, and 22.9 (3.6 – 96.1)/3.3 (0.7 – 9.6) at post-treatment, respectively. Partial or complete responses were seen at 4/7 (57%) and 0/3 (0%) in IL-6 elevated and non-elevated cases, respectively (p=0.048), while 2/6 (33%) and 2/4 (50%) of TNF-α elevated and non-elevated cases showed response (p=0.589). SAEs were significantly frequent in TNF-α elevated cases (3/6 [50%] vs. 0/4 [0%] in non-elevated cases, p=0.048). In 34 patients analyzed for CRP, age was 67 (45 – 89); PS 0/1/2/3: 18/12/2/2; Sqc/Non-Sqc: 14/20; the days before/after anti-PD-1 antibody administration: 1 (0 – 7)/ 3 (2 – 7). CRP was significantly increased after anti-PD-1 antibody administration (1.8 [0.1 – 17.8] mg/dL at pre- and 2.4 [0.0 – 27.8] at post-treatment; p=0.001), and in 31 efficacy-evaluable cases, more responses were recognized in CRP-elevated cases (10/22 [45%]) compared to non-elevated cases (1/9 [11%]), although not statistically significant (p=0.054). SAEs were seen in 5/25 (20%) of CRP-elevated cases vs. 4/9 (44%) of CRP-non-elevated cases (p=0.17).
    
    Conclusion:
    Anti-PD-1 antibody affected inflammatory cytokine production and significantly increased CRP within a week in patients with non-small cell lung cancer. The early induction of inflammatory cytokines after PD-1 antibody administration may have a key role on the induction of anti-cancer immunity and adverse effects.