title: The prognostic value of clonal heterogeneity and quantitative assessment of plasma circulating clonal IG-VDJ sequences at diagnosis in patients with follicular lymphoma.
abstract: Recent advances in next-generation sequencing (NGS) have enabled the quantitation of circulating tumour DNA (ctDNA) encoding the clonal rearranged V(D)J immunoglobulin locus. We aimed to evaluate the clonal heterogeneity of follicular lymphoma (FL) in the tumour and the plasma at diagnosis and to assess the prognostic value of the ctDNA level. Plasma samples at diagnosis were available for 34 patients registered in the PRIMA trial (NCT00140582). One tumour clonotype or more could be detected for 29 (85%) and 25 (74%) patients, respectively, in the tumour or plasma samples. In 18 patients, several subclones were detected in the tumour (2 to 71 subclones/cases) and/or in the plasma (2 to 20 subclones/cases). In more than half of the cases, the distribution of subclones differed between the tumour and plasma samples, reflecting high clonal heterogeneity and diversity in lymphoma subclone dissemination. In multivariate analysis, a high level of ctDNA was the only independent factor associated with patients' progression-free survival (HR 4, IC 95 (1.1-37), p=.039). In conclusion, an NGS-based immunosequencing method reveals the marked clonal heterogeneity of follicular lymphoma in patients with FL, and quantification of ctDNA at diagnosis represents a potential powerful prognostic biomarker that needs to be investigated in larger cohorts.
authors.affiliation: Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Service d'Hématologie, 69495 Pierre Bénite Cedex, France.|NSERM1052, CNRS 5286, Université Claude Bernard, Faculté de Médecine Lyon-Sud Charles Mérieux Lyon-1, 69495 Pierre Bénite Cedex, France.
authors.forename: Clémentine
authors.initials: C
authors.lastname: Sarkozy
authors.affiliation: NSERM1052, CNRS 5286, Université Claude Bernard, Faculté de Médecine Lyon-Sud Charles Mérieux Lyon-1, 69495 Pierre Bénite Cedex, France.|Hospices Civils De Lyon, Laboratoire d'Hématologie, Pierre Bénite, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Huet
authors.affiliation: Adaptive Biotechnologies Corp., South San Francisco, CA, USA.
authors.forename: Victoria E H
authors.initials: VE
authors.lastname: Carlton
authors.affiliation: Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France.
authors.forename: Bettina
authors.initials: B
authors.lastname: Fabiani
authors.affiliation: Service d'Hématologie, CHU de Reims, Reims, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Delmer
authors.affiliation: Centre Henri Becquerel, Service d'Hématologie, Rouen, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jardin
authors.affiliation: Department of Biological Hematology and Immunology, Assistance Publique - Hôpitaux de Paris, Groupe Hospitalier Mondor, Créteil, France.
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Delfau-Larue
authors.affiliation: Centre Hospitalier de Chambery, Service d'Hématologie, Chambery, France.
authors.forename: Maya
authors.initials: M
authors.lastname: Hacini
authors.affiliation: Institut Gustave Roussy, Service d'Hématologie, Université Paris-Sacley, Villejuif, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ribrag
authors.affiliation: Service d'Hématologie, CHU de Poitiers, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Guidez
authors.affiliation: Adaptive Biotechnologies Corp., South San Francisco, CA, USA.
authors.forename: Malek
authors.initials: M
authors.lastname: Faham
authors.affiliation: Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Service d'Hématologie, 69495 Pierre Bénite Cedex, France.|NSERM1052, CNRS 5286, Université Claude Bernard, Faculté de Médecine Lyon-Sud Charles Mérieux Lyon-1, 69495 Pierre Bénite Cedex, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016009:Chi-Square Distribution; D000074141:Circulating Tumor DNA / Q000097:blood / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008224:Lymphoma, Follicular / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D060152:V(D)J Recombination; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D000074141:Circulating Tumor DNA
keywords: circulating tumor DNA; follicular lymphoma; maintenance; prognostic factor; rituximab