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

Autores: Jiménez-Ubieto, A. (Autor de correspondencia); Poza, M.; Martin-Muñoz, A.; Ruiz-Heredia, Y.; Dorado, S.; Figaredo, G.; Rosa-Rosa, J.M.; Rodríguez, A.; Barcena, C.; Navamuel, L.P.; Carrillo, J.; Sánchez, R.; Rufián, L.; Juárez, A.; Rodríguez, M.; Wang, C.; de Toledo, P.; Grande García, Carlos; Mollejo, M.; Casado, L.F.; Calbacho, M.; Baumann, T.; Rapado, I.; Gallardo, M.; Sarandeses, P.; Ayala, R.; Martínez-López, J.; Barrio, S. (Autor de correspondencia)
Título de la revista: LEUKEMIA
ISSN: 0887-6924
Volumen: 37
Número: 3
Páginas: 659-669
Fecha de publicación: 2023
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 center dot 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.