Abstract 5390: High serum interleukin 6 level associates with early death after initiation of treatment with PD-1 inhibitor in advanced NSCLC
Authors: Oya Yuko , Yoshida Tatsuya , Yamaguchi Teppei , Kuroda Hiroaki , Shimizu Junichi , Horio Yoshitsugu , Matsushita Hirokazu , Hida Toyoaki 
Published: September 2020

Anti-PD-1 therapy has been the standard treatment for advanced NSCLC patients. Some patients show durable response, while there are cases that show rapid progression after initiation of ICI treatment, which leads to early death. Therefore, we need a clear biomarker that identifies for early death after initiation of ICI treatment. We reported that CRP is a predictive marker for the efficacy of nivolumab for advanced NSCLC. Among pro-inflammatory cytokines, IL 6 and IL-1β are reported as a poor prognostic factor of cancer patients, and TNFα and INF-γ are reported to be one of the predictors of ICI efficacy.The aim of this study is to investigate the relationship between serum pro-inflammatory cytokines levels and the efficacy of ICI treatment and early death after ICI treatment.

Methods: We retrospectively reviewed the predictive factors of efficacy and early death (death within 3 months after initiation of treatment) in anti-PD-1 monotherapy in all cohort (N=307). Based on the results in all cohort, we investigated the relationship of proinflammatory cytokines (IL-1β, IL6, IL10, INFγ) level in serum before pre-anti PD-1 therapy by Luminex® system and the clinical outcome of anti-PD-1 treatment in cytokine cohort (N=67). Patients with advanced or postoperative recurrence NSCLC who received 1≤ dose of ICI from December 2015 to September 2018 in our institute were included.

Results: Among 307 patients, 45 patients (14.6%) died within 3 months after the initiation of anti-PD-1 therapy in all cohort. The median PFS of ICI treatment was 3.1months (95%CI: 2.5-4.1). EGFR or ALK mutation, poor PS (2≤), PD-L1 negative, high CRP(1.0 mg/dl≤) were identified as predictive factors for shorter PFS using Cox proportional model. Poor PS, high lung immune prognostic index (2≤), low albumin (&lt;3.5mg/dl), and high CRP were identified in multivariate analysis using the log-rank test for early death. In cytokine cohort, high IL6(4ng/dl≤) and high IL-1β(0.5ng/dl) were identified for shorter PFS ([IL-1β]: 3.0 [1.4-4.5] vs 5.9 [1.8-9.6] months, p=0.016, and [IL6]: 1.9 [1.4-2.6] vs. 4.7 [3.0-7.5] months, p=0.008). High IL6 level was identified for the factors of early death after ICI treatment in multivariate analysis (p=0.001). Although IL1β level had no difference in PS and CRP level, IL6 level significantly increased as PS and CRP increased ([PS] 0 to 1, p=0.004, PS1 to 2, p=0.072, and [IL6]: low CRP 19% vs high CRP 86%, p&lt;0.001) .

Conclusions:This analysis demonstrated that serum high IL6 level at baseline associated with the early death after initiation anti-PD-1 treatment and shorter PFS in advanced NSCLC.

Citation Format: Yuko Oya, Tatsuya Yoshida, Teppei Yamaguchi, Hiroaki Kuroda, Junichi Shimizu, Yoshitsugu Horio, Hirokazu Matsushita, Toyoaki Hida. High serum interleukin 6 level associates with early death after initiation of treatment with PD-1 inhibitor in advanced NSCLC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5390.