Titre :

Cell-free DNA sequencing allows the identification of the mutational profile of TFH lymphomas and has a predictive value: a LYSA study

Auteur(s) :

Sako, N. [Auteur]
Hôpital Henri Mondor
Delfau, M. [Auteur]
Hôpital Henri Mondor
Bachy, E. [Auteur]
Hospices Civils de Lyon [HCL]
Morschhauser, Franck [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Cartron, G. [Auteur]
CHU Montpellier = Montpellier University Hospital
Casasnovas, O. [Auteur]
CHU Dijon
Gressin, R. [Auteur]
Centre Hospitalier Universitaire [CHU Grenoble] [CHUGA]
Daguindau, N. [Auteur]
Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
Tournilhac, O. [Auteur]
CHU Clermont-Ferrand
Bouabdallah, K. [Auteur]
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Le Gouill, S. [Auteur]
Institut Curie [Paris]
Andre, M. [Auteur]
Robe, C. [Auteur]
Hôpital Henri Mondor
Dupuis, J. [Auteur]
Hôpital Henri Mondor
De Leval, L. [Auteur]
Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne] [CHUV]
Gaulard, P. [Auteur]
Hôpital Henri Mondor
Lemonnier, F. [Auteur]
Hôpital Henri Mondor

Titre de la manifestation scientifique :

17th International Conference on Malignant Lymphoma

Ville :

Lugano

Pays :

Suisse

Date de début de la manifestation scientifique :

2023-06-13

Titre de la revue :

Hematological Oncology

Éditeur :

Wiley

Date de publication :

2023-06-09

ISSN :

1099-1069

Mot(s)-clé(s) en anglais :

Aggressive T-cell non-Hodgkin lymphoma
Liquid biopsy
Minimal residual disease

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Introduction: TFH lymphomas (TFHL) commonly harbor mutations in TET2, RHOA, DNMT3A and IDH2. While RHOA and IDH2 appear restricted to the neoplastic cells, TET2 and DNMT3A mutations occur in a significant proportion of ...
Lire la suite >Introduction: TFH lymphomas (TFHL) commonly harbor mutations in TET2, RHOA, DNMT3A and IDH2. While RHOA and IDH2 appear restricted to the neoplastic cells, TET2 and DNMT3A mutations occur in a significant proportion of cases in a hematopoietic progenitor cell and can also be detected in B or myeloid cells. Cell-free DNA (cfDNA) sequencing allows the detection of circulating tumor DNA in solid cancers or B-cell lymphomas, with predictive value, but few data exist on cfDNA sequencing in TFHL. Methods: In the frame of the ORACLE study, a phase 3 trial comparing oral azacitidine to investigator choice treatment in relapsed or refractory TFHL patients, we collected tumor biopsies and plasma in streck tube at inclusion, after 3 cycles, and at progression. Tumour and cfDNA were sequenced by NGS using 9 genes, amplicon-based libraries. Median sequencing depth was 2386X in tumor and 3519X in cfDNA. Results: Among patients with confirmed TFHL treated in LYSA centers, we collected 45 samples at inclusion, 16 after cycle 3, and 14 at progression. The median cfDNA concentration at each time point was respectively 7507 (IQR 3418–19414), 5182 (3438–12429), and 15750 (7316–26953) hEG/mL. Results of cfDNA at inclusion and tumor sequencing were compared in 43 patients. Common TET2 mutations were detected in the tumor of 36/43 (84%) and in cfDNA of 33/43 (77%) patients, with a median variant allele frequency (VAF) of 17.75% vs. 9.8% respectively. RHOAG17V was detected in 29/43 (67%, VAF 10%) and in 24/43 (59%, VAF 4.4%), DNMT3A in 13/43 (30%, VAF 17.9%) and 15/73 (35%, VAF 17.9%), and IDH2 in 12/43 (28%, VAF 5.9%) and 8/43 (19%, VAF 5.4%) of tumor biopsies and cfDNA samples respectively. Only one patient had detectable TET2, DNMT3A, IDH2, and RHOA mutations in the cfDNA and not in the tumor biopsy, corresponding to a tumor with low neoplastic cell content. By contrast, 3 patients had DNMT3A mutations, not affecting the R882 residue, detected in the cfDNA but not in the tumor likely corresponding to clonal hematopoiesis not related to the TFHL. We also compared 25 paired cfDNA samples collected at inclusion and after cycle 3 (including progression sample if occurring at cycle 3 or before). In all but one patient, we observed the persistence of TET2 and DNMT3A mutations, even in responding patients, confirming that these mutations are not restricted to neoplastic cells, and suggesting that treatment, especially with 5-azacitidine, does not affect the clonal hematopoiesis. By contrast, among the 14/25 patients with a detectable RHOA mutation in cfDNA at inclusion, progression-free survival was longer in the 4 patients with the disappearance of the RHOA mutations in cfDNA at cycle 3 than in the 10 others (median 29 vs. 3 months, p = 0.01). Conclusion: cfDNA sequencing allowed the detection of the RHOA mutation in 77% of mutated patients, and the disappearance of RHOA mutation at cycle 3 predict prolonged PFS.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille

Collections :

• Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365

Date de dépôt :

2024-09-06T21:04:44Z
2024-09-25T15:48:10Z
2024-09-26T13:26:26Z