Blood-Epigenetic Biomarker Associations with Tumor Immunophenotype in Patients with Urothelial Carcinoma from JAVELIN Bladder 100

Response to immune checkpoint inhibitors (ICIs) is associated with several biological pathways, including tumor immunogenicity and antitumor immunity. Identifying host factors involved in these pathways may guide personalized ICI treatment. We describe the application of chromatin conformation assays to blood from patients with advanced urothelial carcinoma from the phase 3 JAVELIN Bladder 100 trial (NCT02603432). This trial demonstrated a significant survival benefit with avelumab maintenance plus best supportive care (BSC) vs BSC alone following non-progression with platinum-based chemotherapy as first-line therapy. Blood-based chromatin conformation markers (CCMs) were screened for associations with high/low immune effector gene expression in tumors and for interactions with outcomes and tumor mutation burden. Candidate CCMs included genes involved in several immune response pathways, such as POU2F2, which encodes a transcription factor that regulates B-cell maturation. Our findings suggest that polygenic host factors may affect response to ICIs and support further investigation of chromatin conformation assays.