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

作者：Gayaththri Vimalathas, Marcus Høy Hansen, Oriane Cédile, Mads Thomassen, Michael Møller, Sara Kamuk Dahlmann, M. Kjeldsen, Malene Grubbe Hildebrandt, Anne Lerberg Nielsen, Mohammad Naghavi‐Behzad, Lars Edenbrandt, Charlotte Guldborg Nyvold, Thomas Stauffer Larsen · 发表于：Blood Advances · 年份：2025 · DOI：10.1182/bloodadvances.2025016752 · 被引用次数：4 · 研究领域：Cancer Genomics and Diagnostics、Lymphoma Diagnosis and Treatment、Lung Cancer Treatments and Mutations

ABSTRACT: 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.