Monitoring ctDNA in aggressive B-cell lymphoma: a prospective correlative study of ctDNA kinetics and PET-CT metrics

Positron emission tomography-computed tomography (PET-CT) is recommended for response evaluation in aggressive large B-cell lymphoma (LBCL) but cannot detect minimal residual disease (MRD). Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for real-time disease monitoring. This study evaluated longitudinal ctDNA monitoring as an MRD marker in LBCL. In this prospective, single-center study, 14 newly diagnosed patients with LBCL receiving first-line immunochemotherapy underwent frequent longitudinal blood sampling. A 53-gene targeted sequencing panel quantified ctDNA and evaluated its kinetics, correlating it with clinical parameters and PET-CT, including total metabolic tumor volume (TMTV) calculated using artificial intelligence-based analysis via RECOMIA. Baseline ctDNA was detected in 11 of 14 patients (79%) with a median variant allele frequency of 6.88% (interquartile range, 1.19%-10.20%). ctDNA levels correlated significantly with TMTV (ρ = 0.90; P < .0001) and lactate dehydrogenase. ctDNA kinetics, including after 1 treatment cycle, mirrored PET-CT metabolic changes and identified relapsing or refractory patients. This study demonstrates ctDNA-based MRD monitoring in LBCL using a fixed targeted assay with an analytical sensitivity of at least 10-3. The kinetics of ctDNA reflects the clinical course and PET-CT findings, underscoring its complementary potential to PET-CT.