Clinical Implication of Sequential Circulating Tumor DNA Assessments for the Treatment of Diffuse Large B-Cell Lymphoma.

Background/objectives: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for non-invasive tumor monitoring in diffuse large B-cell lymphoma (DLBCL).

Methods: In this study, 52 patients with newly diagnosed advanced-stage DLBCL treated with R-CHOP underwent serial ctDNA analysis at baseline, interim (after three cycles), and end of treatment. The prognostic significance of ctDNA dynamics was evaluated, and its predictive value was compared with the PET/CT response.

Results: Targeted next-generation sequencing revealed baseline ctDNA in 98.1% of patients, with 74.7% concordance to tumor tissue genotyping. Higher baseline ctDNA levels correlated with elevated LDH, older age, and high IPI scores. A ≥2-log reduction in ctDNA at interim was significantly associated with improved overall survival ( = 0.004), though not with progression-free survival. Notably, combining interim ctDNA dynamics with PET/CT results enhanced the predictive accuracy for treatment outcomes, particularly among patients with partial metabolic responses.

Conclusions: These findings support the clinical utility of ctDNA for dynamic risk assessment in DLBCL, and suggest that integrating ctDNA with imaging biomarkers may guide more personalized therapeutic strategies. Further validation using highly sensitive ctDNA assays is warranted to optimize its role in routine clinical practice.