C032 | INTEGRATION OF CIRCULATING BIOMARKERS AND EPIGENETIC AGING IN HODGKIN LYMPHOMA: INSIGHTS FROM A MONOCENTER PROSPECTIVE STUDY

Hodgkin lymphoma (HL) is characterized by rare malignant cells within an inflammatory microenvironment. While most patients achieve remission, a subset experiences relapse or develops refractory disease. This study aims to monitor disease features and assess whether the pace of aging, measured by epigenetic clocks, may be associated with HL clinical outcome. We compared 26 newly-diagnosed HL (ND-HL) patients with 16 in long-term complete remission (LT-CR, ≥2 years), all enrolled at IRCCS Azienda Ospedaliero-Universitaria of Bologna, Istituto di Ematologia "Seràgnoli". For ND-HL patients, peripheral blood was collected prior to first-line therapy. The overall response rate (ORR) was 80.8%, with all responders achieving complete remission (CR, n = 21). Peripheral immune profiling was performed using multicolor flow cytometry with a panel of 46 plasma mediators using a multiplex assay. Circulating microRNAs were sequenced from plasma. DNA methylation was analyzed by array to calculate epigenetic age via established algorithms. ND-HL patients displayed significantly elevated levels of both pro- and anti-inflammatory cytokines (Figure 1A-C), monocyte-activating factors (Figure 1D-F), and classical monocytes (Figure 1G) compared to LT-CR, indicating a myeloid-driven inflammatory signature. Two microRNAs, miR-150-5p and miR-10b-3p, were markedly deregulated in ND-HL and are known to target anti-inflammatory genes such as IL-10. TIMP-1, an immunosuppressive factor implicated in HL, was significantly higher in ND-HL. According to GrimAge epigenetic clock analysis, ND-HL patients appeared biologically older than their chronological age when compared to LT-CR, suggesting that accelerated epigenetic aging may characterize HL. Notably, TIMP-1 is one of the biomarkers integrated into GrimAge clock estimation. Further studies in larger cohorts are warranted to elucidate the biological underpinnings of epigenetic aging in HL and its potential role in risk stratification and prognosis.