Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease

• Published in: British journal of haematology Vol. 205; no. 1; pp. 109 - 121
• Main Authors: Alcoceba, Miguel, Stewart, James P, García-Álvarez, María, Díaz, Luis G, Jiménez, Cristina, Medina, Alejandro, Chillón, M Carmen, Gazdova, Jana, Blanco, Oscar, Díaz, Francisco J, Peñarrubia, María J, Fernández, Silvia, Montes, Carlos, Cabero, Almudena, Caballero, María D, García-Sanz, Ramón, González, Marcos, González, David, Tamayo, Pilar, Gutiérrez, Norma C, García-Sancho, Alejandro Martín, Sarasquete, M Eugenia
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-07-2024
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - blood; Biopsy; Circulating Tumor DNA - blood; Circulating Tumor DNA - genetics; Computed tomography; Cyclophosphamide - administration & dosage; Cyclophosphamide - therapeutic use; Doxorubicin - administration & dosage; Doxorubicin - therapeutic use; Female; Genotyping; High-Throughput Nucleotide Sequencing; Humans; L-Lactate dehydrogenase; Liquid Biopsy - methods; Lymphoma; Lymphoma, Large B-Cell, Diffuse - blood; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - mortality; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Medical prognosis; Middle Aged; Minimal residual disease; Neoplasm, Residual - diagnosis; Patients; Positron emission tomography; Positron Emission Tomography Computed Tomography; Prednisone - administration & dosage; Prednisone - therapeutic use; Prognosis; Rituximab - administration & dosage; Rituximab - therapeutic use; Statistical analysis; Tomography; Vincristine - administration & dosage; Vincristine - therapeutic use; molecular haematology; minimal residual disease; non‐hodgkin lymphoma; liquid biopsy
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/bjh.19458

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.