https://orcid.org/0000-0001-5507-9762
Key Points
ctDNA levels were correlated with PET-CT-based total metabolic tumor volume and may enable earlier relapse detection than imaging alone.
A rapid ~100-fold median reduction in ctDNA was observed by day 8 of the first treatment cycle and mirrored clinical response dynamics
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 LBCL patients 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 AI-based analysis via RECOMIA. Baseline ctDNA was detected in 11 out 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 = 0.91, p < 0.0001) and lactate dehydrogenase. Circulating tumor DNA kinetics, including after one treatment cycle, mirrored PET-CT metabolic changes and identified relapsing or refractory cases. 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.
