Fiche publication
Date publication
mai 2026
Journal
Blood
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SIMAND Célestine
Tous les auteurs :
Duployez N, Joudinaud R, Boudry A, Hunault M, Fenwarth L, Tavernier E, Pautas C, Bertoli S, Tavitian S, Raffoux E, Hospital MA, Marchand T, Heiblig M, Chantepie SP, Carre M, Peterlin P, Gallego-Hernanz MP, Guieze R, Simand C, Turlure P, Huynh A, Lemasle E, Gabellier L, Lambert J, Suarez F, Chraibi S, Sanhes L, Celli-Lebras K, Mineur A, Gardin C, Ifrah N, Vey N, Peffault de Latour R, Rigolot L, Luquet I, Penther D, Itzykson RA, Delabesse E, Hamel-Broza JF, de Botton S, Pigneux A, Dombret H, Récher C, Preudhomme C, Dumas PY
Lien Pubmed
Résumé
FLT3 internal tandem duplications (FLT3-ITD) are major genetic events in acute myeloid leukemia (AML). Although the clinical impact of FLT3-ITD "macroclones" (allelic ratio [AR] ≥0.05) is well established, the significance of low-level FLT3-ITD subclones ("microclones") remains uncertain. We conducted a post-hoc analysis of 1 733 patients with newly diagnosed AML enrolled in the BIG-1 trial (NCT02416388). Using next-generation sequencing (NGS), we detected FLT3-ITD microclones (AR between 0.0004 and 0.05) in 17.4% of patients without FLT3-ITD macroclones. Microclones and macroclones (low and high AR) were independently associated with increased relapse risk (sHR 1.50 [95% CI 1.18-1.91], 1.98 [1.50-2.62], and 2.33 [1.69-3.22], respectively) after adjustment for age, white blood cell count, other gene mutations, midostaurin treatment, and allogeneic hematopoietic stem cell transplantation. At 2 years, cumulative incidence of relapse reached 42.5% (95% CI 37.0-47.9) in patients with macroclones, 45.1% (38.3-51.6) in patients with microclones, and 29.4% (26.6-32.3) in patients without FLT3-ITD. In NPM1-mutated AML, both microclones and macroclones were associated with higher levels of measurable residual disease (MRD) and increased relapse risk, without independent impact on overall survival after adjustment for MRD. Analysis of paired samples further revealed that 41.8% of relapses in patients with FLT3-ITD microclones at diagnosis were associated with a macroclone at relapse. These findings challenge current risk stratification models and support the integration of NGS-based FLT3-ITD detection into the diagnostic and prognostic workflow for AML. Prospective trials addressing the management of patients with FLT3-ITD microclones are warranted, as is their consideration in future ELN guidelines.
Référence
Blood. 2026 05 21;:
