Prognostic utility of circulating tumor DNA in classical hodgkin lymphoma: A systematic review and individual participant data bayesian meta-analysis.

Over 20 % of patients with Hodgkin lymphoma (HL) experience disease progression after initial treatment. We evaluated the prognostic utility of circulating tumor DNA (ctDNA) in HL patients. We systematically searched PubMed, Embase, the Cochrane Library, Scopus, and Web of Science up to March 22, 2025. Survival data were extracted from Kaplan-Meier curves and digitized to reconstruct individual patient-level datasets. We applied a hierarchical Bayesian model with weakly informative priors to estimate hazard ratios (HRs), restricted mean survival times (RMSTs), along with their 95 % credible intervals (CrI) up to five years for both progression-free survival (PFS) and overall survival (OS). Ten studies, including 1158 patients, were analyzed. Elevated baseline ctDNA was associated with inferior PFS (HR: 2.74; 95 % CrI: 1.30-5.75) and a 5-year RMST loss of 7.7 (1.2-17.3) months. Prognostic strength increased over time, with interim ctDNA positivity showing an HR of 5.99 (3.46-10.13; ΔRMST: 22.7 months; 12.9-33.2) and end-of-treatment ctDNA positivity showing an HR of 13.4 (3.97-41.87; ΔRMST: 39.2 months; 17.7-49.4). High baseline ctDNA was associated with worse OS (HR: 2.49; 1.07-5.80; ΔRMST: 11.6 months; 0.7-27.8). Similarly, positive ctDNA following treatment predicted worse OS (HR: 4.74; 1.60-14.47; ΔRMST: 16.2 months; 3.0-38.1). To conclude, in HL patients, a higher ctDNA concentration was associated with increased disease progression and mortality, with this association intensifying toward the end-of-treatment. Clinical implementation requires standardization of assay methods, validation of prognostic thresholds, and longitudinal assessment of the independent prognostic value of ctDNA.