Journal Article

Real-life disease monitoring in follicular lymphoma patients using liquid biopsy ultra-deep sequencing and PET/CT

Baumann, Tycho, Rodriguez, Margarita, Casado, Luis-Felipe, Sarandeses, Pilar, Mollejo, Manuela, Poza, María, Carrillo, Jaime, Figaredo, Gloria, Martínez-López, Joaquín, Rosa-Rosa, Juan Manuel, Rapado, Inmaculada, Sanchez, Ricardo, Juárez, Alexandra, Barcena, Carmen, Navamuel, Laura Parrilla, Rufian, Laura, Ruiz-Heredia, Yanira, Ayala, Rosa, Martin-Muñoz, Alejandro, Wang, Chongwu, Gallardo, Miguel, Dorado, Sara, Grande, Carlos, Calbacho, María, Barrio, Santiago, de Toledo, Paula, Jiménez-Ubieto, Ana, Rodriguez, Antonia

2023

Overview

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 used an ultra-deep sequencing approach with 2 · 10−4 sensitivity (LiqBio-MRD) to track those mutations on 151 follow-up liquid biopsy samples from 54 treated patients. Positive LiqBio-MRD at first-line therapy correlated with a higher risk of progression both at the interim evaluation (HRINT 11.0, 95% CI 2.10–57.7, p = 0.005) and at the end of treatment (HREOT, HR 19.1, 95% CI 4.10–89.4, 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 identified the patients that progressed in less than two years with 88% sensitivity and 100% specificity. 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 response-adapted clinical trials.

• Publisher: Nature Publishing Group
• Subject: Biomarkers / Biopsy / Clinical trials / Computed tomography / Health services / Lymph nodes / Lymphoma / Mutation / Next-generation sequencing / Patients / Sensitivity