Publicaciones científicas

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

03-ene-2023 | Revista: Leukemia

Ana Jiménez-Ubieto #  1 , María Poza #  2 , Alejandro Martin-Muñoz  3 , Yanira Ruiz-Heredia  2   3 , Sara Dorado  3   4 , Gloria Figaredo  5 , Juan Manuel Rosa-Rosa  2 , Antonia Rodriguez  2 , Carmen Barcena  6 , Laura Parrilla Navamuel  5 , Jaime Carrillo  3 , Ricardo Sanchez  2   3 , Laura Rufian  2   3 , Alexandra Juárez  2   3 , Margarita Rodriguez  2   3 , Chongwu Wang  7 , Paula de Toledo  4 , Carlos Grande  8 , Manuela Mollejo  5 , Luis-Felipe Casado  5 , María Calbacho  2 , Tycho Baumann  2 , Inmaculada Rapado  2 , Miguel Gallardo  2   9 , Pilar Sarandeses  10 , Rosa Ayala  2 , Joaquín Martínez-López #  2 , Santiago Barrio #  11   12


Abstract

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.

CITA DEL ARTÍCULO  Leukemia. 2023 Jan 3.  doi: 10.1038/s41375-022-01803-x