Pretherapeutic inflammation status and cytokine profile may predict response to immunotherapy in NSCLC patients

Abstract

Background: NSCLC accounts for about 85% of all diagnosed lung cancers. As most patients need systemic treatment and immunotherapy is now current standard in second line treatment and will also establish in first line therapy, many patients receive immunotherapy. Pretherapeutic markers to identify patients who will respond to immunotherapy are required, also regarding to the immense costs. Accordingly, this study aims at examining the pretherapeutic inflammation status as well as the cytokine profile of patients who receive immunotherapy with Nivolumab. Methods:We analyzed 37 patients withNSCLC treated withNivolumab at a German lung cancer center between 2015 und 2016.We extracted data sets fromelectronic patient records and compared anthropometric data, pretherapeutic blood values and prognostic scores (neutrophil to lymphocyte ratio (NLR), Systemic Inflammation Index (SII), Prognostic Nutritional Index (PNI) and the Glasgow Prognostic Score (GPS)). Blood samples of 16 patients were analyzed using a cytokine ELISA (IL-4, IL-6, IL-10 and IFNc). Results: Patients, who did not respond to Nivolumab treatment showed significant elevated pretherapeutic markers of acute inflammation (NLR p=0.006; CRP p=0.001; SII p=0.017; GPS p=0.011; PNI p=0.004). Examination of cytokine profile revealed that most patients with primary progression had at least one elevated marker of (i) acute inflammation (IL-6) or (ii) suppressed T-cell response (IL-10). Elevated IFNc was associated with response to immunotherapy, whereas in combination with increased IL-6, INFc showed to characterize patients with primary progression. Patients who progressed after initial response, showed increasing IL-6, IL-10 or decreasing IFNc values. Conclusions: NSCLC patients with pretherapeutic acute inflammation status or T-cell suppressing cytokine profile showed significant worse response to immunotherapy with Nivolumab. Pretherapeutic assessment of inflammation status could cost-effectively identify patients who benefit from immunotherapy. Thus, monitoring of cytokine profile under Nivolumab treatment could discriminate between stable disease, pseudoprogression or real progressive disease., , , ,.