Abstract LB-143: Th1/Th2 and inflammatory cytokines as biomarkers of response to ipilimumab in small cell lung cancer (SCLC) patients
Authors: Hardy-Werbin Max , Rocha Pedro , Arpí Oriol , Taus Álvaro , Jordà Xavier Durán , Joseph-Pietras Deborah , Rovira Ana , Albanell Joan , Ottensmeier Christian , Arriola Edurne 
Published: August 2018

Ipilimumab appears to benefit a subset of patients with SCLC but no predictive marker is available to date. Cytokines encompass a group of pleiotropic proteins secreted by immune and cancer cells with a crucial role in immune response (Th1/Th2 balance). Our study sought to evaluate the role of serum cytokine levels and changes during treatment as biomarkers of outcome with ipilimumab in SCLC.

Serial serum samples (pre and on-treatment at 9 weeks) from two cohorts (C) of patients with recently diagnosed SCLC were evaluated in this study. C1, with 47 patients treated with first-line platinum/etoposide (PE) and C2, with 37 patients treated with PE plus ipilimumab (10mg/kg) within the ICE trial. By means of a fluorescent multiplex immunobead assay (Luminex Technology) we analyzed serum concentrations of Th1 (IL-2, IFN-γ), Th2 (IL-4, -5, -6, -10) and inflammatory (IL-1β, IL-8, GM-CSF, TNF-α, MIP1-α) cytokines. Optimal cut-offs were determined by the Contal and O'Quigley method. We evaluated the associations of cytokine baseline levels and on-treatment changes with patient outcomes and compare these between cohorts. Statistical analysis was carried out with Stata/MP 14 (StataCorp LLC) and Prism 6.0 (GraphPad).

In the ipilimumab cohort, patients with increased baseline levels of IL-2 (&gt;1.67 pg/mL) showed a median overall survival (OS) of 24.2 months (m) (9.5-not reached) vs. those with lower levels [7.9m (5.6-18.46); p=0.030]. On the contrary, those with higher levels of IL-6 (&gt;3.74 pg/mL) or TNF-α (&gt;9.17 pg/mL) had worse OS (9.5m vs. 18.5m; p=0.019 and 7.8 vs. 18.5m; p=0.003, respectively). Lastly, patients whose IL-8 levels decreased from baseline to the on-treatment time-point (ICE) by more than 28.3%, had a worse OS [7.9m (3.9-17) vs. 18.46m (9.5-30.5); p=0.008]. The rest of associations observed were common between both cohorts.

Serum levels of Th1/Th2 and inflammatory cytokines change during treatments in SCLC patients. Having a ‘control' cohort of SCLC patients treated with chemotherapy allowed us to specifically identify differential changes induced by ipilimumab. Our study suggests that cytokines could be explored as biomarkers of sensitivity (IL-2) or resistance (IL-6 and TNF-α) to ipilimumab when combined with chemotherapy. Changes of cytokine levels during treatment might also predict benefit (IL-8). These findings warrant prospective validation.

Citation Format: Max Hardy-Werbin, Pedro Rocha, Oriol Arpí, Álvaro Taus, Xavier Durán Jordà, Deborah Joseph-Pietras, Ana Rovira, Joan Albanell, Christian Ottensmeier, Edurne Arriola. Th1/Th2 and inflammatory cytokines as biomarkers of response to ipilimumab in small cell lung cancer (SCLC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-143.