In the present study, we screened 84 Follicular Lymphoma patients for somatic mutations suitable as liquid biopsy MRD biomarkers using a targeted next-generation sequencing (NGS) panel. We found trackable mutations in 95% of the lymph node samples and 80% of the liquid biopsy baseline samples.Then, we use an ultra-deep sequencing approach with 2 • 10 − 4 sensitivity (LiqBio-MRD) to track those mutations on 156 follow-up liquid biopsy samples from 55 treated patients. Positive LiqBio-MRD correlated with a higher risk of progression both at the interim evaluation (HR 13.0, 95% CI 2.70-63.4, p < 0.001) and at the end of treatment (EOT, HR 14.3, 95% CI 4.4-46.4, p < 0.001). Similar results were observed by PET/CT Deauville score, with a median PFS of 19 months vs. NR (p < 0.001) at the interim and 13 months vs. NR (p < 0.001) at EOT. LiqBio-MRD and PET/CT combined identi ed the patients that progressed in less than two years with 89% sensitivity and 100% speci city. Our results demonstrate that LiqBio-MRD is a robust and non-invasive approach, complementary to metabolic imaging, for identifying FL patients at high risk of failure during the treatment and should be considered in future responseadapted clinical trials.
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.
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