Genetic Profiling of Cell-Free DNA in Liquid Biopsies: A Complementary Tool for the Diagnosis of B-Cell Lymphomas and the Surveillance of Measurable Residual Disease

SIMPLE SUMMARY: Genetic profiling of plasma cell-free DNA (cfDNA) from liquid biopsies (LiqBio) is a possible alternative to genetic profiling of tissue biopsies to diagnose B-cell lymphoma (BCL), and a complementary tool of PET/CT to determine measurable residual disease (MRD). The aim of our study was to confirm the utility of LiqBio for diagnosis and surveillance of BCL. We confirmed the correlation between somatic mutations in paired LiqBio and tissue biopsies at diagnosis in a population of 78 patients; furthermore, we identified additional mutations in LiqBio at diagnosis from patients with no available tissue samples or no mutations detected in tissue samples. As a surveillance tool for MRD detection, LiqBio combined with PET/CT showed to be a valuable method, improving the PET/CT specificity. ABSTRACT: Purpose: To assess the potential value of LiqBio as a complementary tool for diagnosis and surveillance of BCL. Methods: This prospective multi-center study included 78 patients (25 follicular lymphomas (FL) and 53 large B-cell lymphomas (LBCL)). We performed next-generation sequencing (NGS) of cfDNA LiqBio and paired gDNA tissue biopsies at diagnosis and compared the mutational statuses. Also, through NGS of LiqBio, we identified MRD biomarkers and compared this novel LiqBio–MRD method with PET/CT in detecting MRD at follow-up. Results: We identified mutations in 71% of LiqBio and 95% of tissue biopsies, and found a correlation between variant allele frequency of somatic mutations. Additionally, we identified mutations in 73% of LiqBio from patients with no available tissue samples or no mutations in them. Regarding the utility of LiqBio–MRD as a dynamic monitoring tool, when compared with the PET/CT method, a lower sensitivity was observed for LiqBio–MRD at 92.3% (vs. 100% for PET/CT), but a higher specificity of 91.3% (vs. 86.9% for PET/CT). Conclusion: Genetic profiling of tumor cfDNA in plasma LiqBio is a complementary tool for BCL diagnosis and MRD surveillance.