{Reference Type}: Journal Article {Title}: Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease. {Author}: Alcoceba M;Stewart JP;García-Álvarez M;Díaz LG;Jiménez C;Medina A;Chillón MC;Gazdova J;Blanco O;Díaz FJ;Peñarrubia MJ;Fernández S;Montes C;Cabero A;Caballero MD;García-Sanz R;González M;González D;Tamayo P;Gutiérrez NC;García-Sancho AM;Sarasquete ME; {Journal}: Br J Haematol {Volume}: 205 {Issue}: 1 {Year}: 2024 Jul 29 {Factor}: 8.615 {DOI}: 10.1111/bjh.19458 {Abstract}: Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.