Supporting data for "Longitudinal Monitoring of Circulating Tumor DNA in Aggressive Large 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 the longitudinal monitoring of ctDNA 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, PET-CT response, and total metabolic tumor volume (TMTV) calculated via AI-based RECOMIA analysis.

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 significantly correlated with TMTV (ρ = 0.91, p < 0.0001) and tumor burden markers. In responders, ctDNA declined by 2-log-fold after one cycle. In responders, the 1–2 log10-fold reduction in ctDNA levels after one cycle of treatment mirrored the PET-CT metabolic changes. Concurrently with PET-CT, ctDNA levels identified all relapse or refractory disease cases.

This study demonstrates ctDNA-based MRD monitoring in LBCL using a clinically applicable targeted assay with a minimum analytical sensitivity of 10-3. The kinetics of ctDNA reflected the clinical course and PET-CT response, correlating strongly with AI-based TMTV, underscoring its complementary potential to PET-CT.