Biomarker study on pneumonitis in durvalumab maintenance therapy after chemoradiotherapy for stage III non-small cell lung cancer

The standard treatment for stage III non-small cell lung cancer (NSCLC) is platinum-based concurrent chemoradiotherapy (CCRT), followed by durvalumab (anti-programmed death ligand-1 antibody) maintenance therapy. Biomarkers related to immune-related pneumonitis during durvalumab maintenance therapy after CCRT for stage III NSCLC have not yet been identified. We evaluated 88 cytokines/chemokines at three time points, before concurrent chemoradiotherapy (pre-CCRT), post-radiotherapy, and six weeks after durvalumab administration, using a multiplex assay (Bio-Plex system) in 29 patients who provided consent for the blood biomarker study, categorizing them into Grade 0–1 and Grade 2 or higher pneumonitis groups. At pre-CCRT, no significant changes were observed; however, at post-radiotherapy, significant changes in TNFRSF8/sCD30 were observed in the group with Grade 2 or higher pneumonitis. Moreover, six weeks after durvalumab administration, significant changes were observed in TNFRSF8/sCD30, in addition to TNFSF12, IL-1Ra, CXCL9/CXCL10/CXCL11, IFN-γ, and CCL19. Although no biomarkers predicting Grade 2 or higher pneumonitis before CCRT were identified, the relationship between radiotherapy and TNFRSF8/sCD30 as well as the relationship between durvalumab administration and various cytokines/chemokines is reported for the first time in stage III NSCLC. In particular, the CXCL family, including CXCL9, CXCL10, and CXCL11, is considered highly significant in pneumonitis with durvalumab maintenance therapy after CCRT for stage III NSCLC. Further large-scale studies are needed to establish biomarkers for patients with NSCLC who receive durvalumab maintenance therapy after CCRT.