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