Non-invasive monitoring of diffuse large B-cell lymphoma by cell-free DNA high-throughput targeted sequencing: analysis of a prospective cohort

Abstract

From a liquid biopsy, cell-free DNA (cfDNA) can provide information regarding basal tumoral genetic patterns and changes upon treatment. In a prospective cohort of 30 diffuse large B-cell lymphomas (DLBCL), we determined the clinical relevance of cfDNA using targeted next-generation sequencing and its correlation with PET scan imaging at the time of diagnosis and during treatment. Using a dedicated DLBCL panel, mutations were identified at baseline for 19 cfDNAs and profiles were consistent with expected DLBCL patterns. Tumor burden-related clinical and PET scan features (LDH, IPI, and metabolic tumor volume) were significantly correlated with the quantity of tumoral cfDNA. Among the four patients presenting additional mutations in their cfDNAs, three had high metabolic tumor volumes, suggesting that cfDNA more accurately reflects tumor heterogeneity than tissues biopsy itself. Mid-treatment, four patients still had basal mutations in their cfDNAs, including three in partial response according to their Deauville scores. Our study highlights the major interests in liquid biopsy, in particular in the context of bulky tumors where cfDNA allows capturing the entire tumoral mutation profile. Therefore, cfDNA analysis in DLBCL represents a complementary approach to PET scan imaging.

Targeted genotyping of circulating tumor DNA for classical Hodgkin lymphoma monitoring: a prospective study

“…In median value, 4 somatic variants per mutated patient [1][2][3][4][5][6][7][8][9][10][11][12] were identified. The entire coding sequence of SOCS1 was sequenced and is the most frequently mutated gene in this study with 55 somatic variants identified in gDNA and/or ctDNA of 30 patients (50%), some thus presenting 2 (or more) somatic variants but there is no recurrent variant identified for this gene.…”

“…Patients with favorable localized stage I-II disease received 2 cycles of ABVD (doxorubicin, bleomycin, vinblastin, dacarbazine) followed by 20-Gray involved-field radiotherapy (IFRT); unfavorable localized stage I-II received 4 cycles of ABVD followed by 30-Gray IFRT 10,11 .…”

Oncogenic Mutations of MYD88 and CD79B in Diffuse Large B-Cell Lymphoma and Implications for Clinical Practice

“…An alternative technique for ctDNA analysis is represented by next-generation sequencing (NGS). The benefit of this technique over ddPCR is the possibility of identifying multiple variants, as shown by two studies in DLBCL patients [ 74 , 75 ].…”

MYD88 in the driver’s seat of B-cell lymphomagenesis: from molecular mechanisms to clinical implications

“…31,138 An alternative technique for ctDNA analysis is targeted next-generation sequencing. The benefit of this technique over ddPCR is the possibility of identifying multiple variants at the same time, as was shown by Bohers et al 139 and Kurtz et al 140 in liquid biopsies from 30 and 217 DLBCL patients, respectively. The mutational burden of most of their patients, with a median of 117 variants per patient, was sufficient for disease monitoring.…”

“…In their studies, the tumor burden, as measured by positron emission tomographycomputed tomography scans, was significantly correlated with the variant allele frequency of ctDNA both during and after treatment. 139,140 Given this recent progress in ctDNA analysis, liquid biopsies are a minimally invasive method for evaluation of the molecular profile and can be used for analysis of tumor burden, disease progression, and treatment efficacy in patients with B-NHL.…”