Prognostic Impact of FLT3 ‐ ITD Allelic Ratio in AML Patients Treated With High‐Dose Anthracycline and a FLT3 Inhibitor
The prognostic value of FLT3 internal tandem duplication (FLT3-ITD) in acute myeloid leukemia (AML) has traditionally been stratified according to the ITD/wild-type allelic ratio (AR) and NPM1 co-mutation status. We evaluated the prognostic impact of FLT3-ITD AR in 459 newly diagnosed AML patients younger than 60 years enrolled in the prospective BIG-1 study, all treated with high-dose anthracycline-based induction. From 2018 onward, midostaurin was added for FLT3-mutated cases. AR was not associated with composite complete remission (81.7% vs. 79.6% in low vs. high AR, p = 0.85), overall survival (OS) (median 7.6 vs. 6.9 years, p = 0.25), relapse-free survival (median 2.0 vs. 1.7 years, p = 0.50), or event-free survival (median 1.4 vs. 1.2 years, p = 0.58). In multivariable analyses, only midostaurin exposure (adjusted hazard ratio [aHR] 0.69, 95% CI 0.50-0.95, p = 0.024) and adverse ELN-2022 risk (aHR 1.66, 95% CI 1.18-2.34, p = 0.004) were independently associated with OS. Allogeneic hematopoietic stem cell transplantation was associated with improved relapse-free (aHR 0.40, 95% CI 0.29-0.55, p < 0.001) and event-free survival (aHR 0.37, 95% CI 0.27-0.51, p < 0.001), but not OS. These results indicate that FLT3-ITD AR has no independent prognostic impact in younger AML patients treated with intensive anthracycline-based chemotherapy and midostaurin in contemporary clinical practice.
Authors
- Hervé Dombret (ORCID: https://orcid.org/0000-0002-5454-6768)
- Laurence Sanhès (ORCID: https://orcid.org/0000-0003-1207-7665)
- Arnaud Pigneux (ORCID: https://orcid.org/0000-0001-5479-0261)
- Raphaël Itzykson (ORCID: https://orcid.org/0000-0003-2139-6262)
- Maël Heiblig (ORCID: https://orcid.org/0000-0003-1682-8657)
- Emmanuelle Tavernier (ORCID: https://orcid.org/0000-0002-1447-8721)
- Éric Delabesse (ORCID: https://orcid.org/0000-0002-0928-0753)
- Christian Récher (ORCID: https://orcid.org/0000-0002-3332-4525)
- Isabelle Luquet (ORCID: https://orcid.org/0000-0001-7891-5727)
- Stéphane de Botton (ORCID: https://orcid.org/0000-0002-8126-4942)
- Claude Preudhomme (ORCID: https://orcid.org/0000-0002-1267-9546)
- Étienne Audureau (ORCID: https://orcid.org/0000-0002-6166-149X)
- Pierre‐Yves Dumas (ORCID: https://orcid.org/0000-0003-0119-3548)
- Sylvain Chantepie (ORCID: https://orcid.org/0000-0003-0457-2252)
- Pierre Péterlin (ORCID: https://orcid.org/0000-0001-5463-6686)
- Pascal Turlure
- Romain Guièze (ORCID: https://orcid.org/0000-0001-7563-580X)
- Émilie Lemasle (ORCID: https://orcid.org/0000-0003-3212-1010)
- Felipe Suárez (ORCID: https://orcid.org/0000-0002-3537-9052)
- Sarah Bertoli (ORCID: https://orcid.org/0000-0003-1084-2781)
- Anne Huynh (ORCID: https://orcid.org/0000-0001-8462-6198)
- Lucie Rigolot (ORCID: https://orcid.org/0009-0001-1275-5422)
- Cécile Pautas (ORCID: https://orcid.org/0000-0002-3385-6484)
- Samy Chraïbi (ORCID: https://orcid.org/0000-0001-5722-6017)
- Norbert Vey (ORCID: https://orcid.org/0000-0001-7027-040X)
- Claude Gardin (ORCID: https://orcid.org/0000-0001-9934-3748)
- Karine Celli‐Lebras (ORCID: https://orcid.org/0000-0002-0004-8659)
- Célestine Simand (ORCID: https://orcid.org/0000-0002-2643-358X)
- Emmanuel Raffoux (ORCID: https://orcid.org/0000-0003-3925-7391)
- Mathieu Leclerc (ORCID: https://orcid.org/0000-0003-1093-802X)
- Juliette Lambert (ORCID: https://orcid.org/0000-0001-5142-0310)
- Thomas Cluzeau (ORCID: https://orcid.org/0000-0002-6745-1127)
- Régis Peffault de Latour (ORCID: https://orcid.org/0000-0001-6222-4753)
- Maria-Pilar Gallego-Hernanz
- Ludovic Gabellier (ORCID: https://orcid.org/0000-0003-0663-8083)
- Nicolas Duployez (ORCID: https://orcid.org/0000-0002-3927-1022)
- Ariane Mineur (ORCID: https://orcid.org/0009-0007-7982-641X)
- Martin Carré (ORCID: https://orcid.org/0000-0001-5834-7654)
- Tony Marchand (ORCID: https://orcid.org/0000-0003-4932-2169)
- Jean‐François Hamel
- Dominique Penther (ORCID: https://orcid.org/0000-0003-1775-344X)
- Jean‐Valère Malfuson
- Mathilde Hunault
Institutions
- Hôpital Necker-Enfants Malades (FR)
- Université de Bordeaux (FR)
- Inserm (FR)
- Centre Hospitalier Universitaire de Grenoble (FR)
- Institut Gustave Roussy (FR)
- Centre Hospitalier Universitaire de Bordeaux (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Centre Hospitalier Universitaire de Nantes (FR)
- Centre Hospitalier Universitaire de Toulouse (FR)
- Centre Hospitalier de Perpignan (FR)
- Centre Hospitalier Universitaire de Montpellier (FR)
- Acute Leukemia French Association (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Institut universitaire du cancer de Toulouse Oncopole (FR)
- Hospices Civils de Lyon (FR)
- Centre Hospitalier Universitaire de Nîmes (FR)
- Laboratoire de Thermique et Energie de Nantes (FR)
- Centre Hospitalier Universitaire de Poitiers (FR)
- Centre Hospitalier Universitaire d'Angers (FR)
- Centre Hospitalier Universitaire de Caen Normandie (FR)
- Hôpital l'Archet (FR)
- Centre Hospitalier Universitaire de Limoges (FR)
- Hôpital André Mignot (FR)
- Centre d'Investigation Clinique de Nantes (FR)
- Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
- Hôpital Avicenne (FR)
- Hôpitaux Universitaires Henri-Mondor (FR)
- Hôpital d'instruction des Armées Percy (FR)
- Laboratoire National Henri Becquerel (FR)
- Hôpital Saint-Louis (FR)
- Institut Paoli-Calmettes (FR)
- Centre Hospitalier Universitaire de Rennes (FR)
- Centre Hospitalier Universitaire de Saint-Étienne (FR)
- Centre Hospitalier de Versailles (FR)
- Institut Mondor de Recherche Biomédicale (FR)
- Hôpital Civil, Strasbourg (FR)
- Centre Henri Becquerel (FR)
- Université de Toulouse (FR)
- BoRdeaux Institute of onCology (FR)
- Université de Strasbourg (FR)
- Université de Caen Normandie (FR)
Publication Details
- Journal
- American Journal of Hematology
- Published
- 2026-10-26
- DOI
- https://doi.org/10.1002/ajh.70540
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00