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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 · 10−4sensitivity (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 (HRINT11.0, 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.

Heredia: Altum sequencing: Current Employment. Rufian:Altum sequencing: Current Employment. Carrillo:Altum sequencing: Current Employment. Wang:Hosea Precision Medical Technology Co., Ltd: Current Employment. Canales:Janssen: Honoraria; Karyopharm: Honoraria; Celgene: Honoraria; Takeda: Speakers Bureau; Sandoz: Honoraria; Janssen: Speakers Bureau; Novartis: Honoraria; Sandoz: Speakers Bureau; Janssen: Speakers Bureau; Takeda: Speakers Bureau; Roche: Honoraria; iQone: Honoraria; Janssen: Honoraria; Sandoz: Honoraria; Novartis: Honoraria; Roche: Honoraria; Roche: Speakers Bureau; Karyopharm: Honoraria; Gilead: Honoraria; Sandoz: Speakers Bureau; Roche: Speakers Bureau. Martinez-López:Janssen, BMS, Sanofi, Novartis, Incyte, F. Hoffmann-La Roche and Amgen: Honoraria, Other: Advisory boards; Janssen, Novartis, BMS, Incyte: Consultancy; Hosea and Altum: Membership on an entity's Board of Directors or advisory committees.

Follicular lymphoma (FL) is considered an indolent disorder with a relatively favourable course. With modern day treatments, long remissions are often achieved both in front-line and relapsed settings. However, a subset of patients has a more aggressive course and a poorer outcome. Both, PET-CT and minimal residual disease (MRD) evaluation by PCR defines groups of patients with different prognoses. MRD measurement by NGS is being studied to predict relapse prior to diagnostic imaging in large B cell lymphoma; however, it has never been used in FL. The aim of the present study is to validate a sensitive and standardizable approach to measure liquid Biopsy MRD (LiqBio-MRD) by NGS with >90% applicability and 2E-4 resolution, and to analyse its prognostic impact in FL patients.

Introduction

Introduction:Bone marrow biopsies (BMB) are usually performed before/after therapy to confirm complete response (CR) in follicular lymphoma (FL) patients. Up to 60% of patients may have bone marrow infiltration, that can change Ann Arbor stage, assigning the highest disease stage. Also, BMB infiltration is included in several prognostic indexes such as FLIPI2 and PRIMA-PI. Persistence of bone marrow disease after treatment is associated with worse outcome.

Background:Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of aggressive B-cell lymphoma. Most relapses occur within the first few months resulting in a dismal prognosis; therefore, it's important to identify primary chemorefractory patients at an early stage, to improve their prognosis. Our group have demonstrated that Circulating Tumor DNA (ctDNA) detected by deep sequencing (DeepSeq) constitute a new non-invasive marker for monitoring response in follicular lymphoma (Jimenez-Ubieto A. et al. ASH 2020). CtDNA monitoring in PMBCL might help to better assess therapeutic response, correct false positive PET/CT results due to residual uptake of the mediastinum and define patients who will benefit from radiation therapy (RT). Here we analyzed the potential value of ctDNA monitoring in 11 PMBCL treated with R-DA-EPOCH between 2018-2020 in the Hospital 12 de Octubre.

Martín-Muñoz: Altum sequencing: Current Employment. Dorado: Altum sequencing: Current Employment. Heredia: Altum sequencing: Current Employment, Current equity holder in publicly-traded company. Rufian: Altum sequencing: Current Employment. Canales: Incyte: Consultancy; iQone: Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Sanofi: Consultancy; Eusa Pharma: Consultancy, Honoraria; Sandoz: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Speakers Bureau; Gilead/Kite: Consultancy, Honoraria. Juarez: Altum sequencing: Current Employment. Sanchez: Altum sequencing: Current Employment. López-Muñoz: Amgen: Consultancy. Ayala: Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria; Celgene: Honoraria. Martínez-López: Janssen, BMS, Novartis, Incyte, Roche, GSK, Pfizer: Consultancy; Roche, Novartis, Incyte, Astellas, BMS: Research Funding. Barrio: Altum sequencing: Current Employment, Current equity holder in publicly-traded company.