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Publications

Journal Article Ahead of print

PubMed: 42934825 DOI: 10.1002/ajh.70540

Prognostic Impact of FLT3-ITD Allelic Ratio in AML Patients Treated With High-Dose Anthracycline and a FLT3 Inhibitor.

Am J Hematol

Authors: Mathieu Leclerc, Etienne Audureau, Nicolas Duployez, Mathilde Hunault, Emmanuelle Tavernier, Cécile Pautas, Sarah Bertoli, Emmanuel Raffoux, Marie-Anne Hospital, Tony Marchand, Maël Heiblig, Sylvain Chantepie, Martin Carre, Pierre Peterlin, Maria-Pilar Gallego-Hernanz, Romain Guieze, Célestine Simand, Pascal Turlure, Anne Huynh, Emilie Lemasle, Ludovic Gabellier, Juliette Lambert, Felipe Suarez, Samy Chraibi, Laurence Sanhes, Karine Celli-Lebras, Ariane Mineur, Claude Gardin, Jean-Valère Malfuson, Thomas Cluzeau, Norbert Vey, Régis Peffault de Latour, Lucie Rigolot, Isabelle Luquet, Dominique Penther, Raphael Itzykson, Eric Delabesse, Jean-François Hamel, Stéphane de Botton, Arnaud Pigneux, Hervé Dombret, Claude Preudhomme, Christian Recher, Pierre-Yves Dumas

Affiliations

  • Hematology and Cell Therapy Department, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France.
  • Public Health Department, Clinical Research Unit (URC) Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, IMRB U955 INSERM, Créteil, France.
  • Hematology Laboratory, CHU de Lille, Lille, France.
  • Department of Hematology, CHU d'Angers, Angers, France.
  • Hematology and Cell Therapy Department, CHU de Saint-Etienne, Saint-Etienne, France.
  • Université de Toulouse, CHU de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Service d'Hématologie, Toulouse, France.
  • Department of Hematology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Department of Hematology, Institut Paoli-Calmettes, Marseille, France.
  • Department of Hematology, CHU de Rennes, Rennes, France.
  • Department of Hematology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France.
  • Department of Hematology, CHU de Caen, Caen, France.
  • Department of Hematology, CHU de Grenoble, Grenoble, France.
  • Department of Hematology, CHU de Nantes, Nantes, France.
  • Department of Hematology, CHU de Poitiers, Poitiers, France.
  • Department of Hematology, CHU Estaing, Clermont-Ferrand, France.
  • Department of Hematology, CHU de Strasbourg, Strasbourg, France.
  • Department of Hematology, CHU de Limoges, Limoges, France.
  • Department of Hematology, Centre Henri Becquerel, Rouen, France.
  • Department of Clinical Hematology, CHU de Montpellier, Montpellier, France.
  • Department of Hematology, Hôpital Mignot, Centre Hospitalier de Versailles, Versailles, France.
  • Department of Adult Hematology, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Department of Hematology, CHU de Nîmes, Nîmes, France.
  • Department of Hematology, Centre Hospitalier de Perpignan, Perpignan, France.
  • Acute Leukemia French Association Group Coordination, IRSL, Paris, France.
  • French Innovative Leukemia Organization Group Coordination, CHU de Bordeaux, Bordeaux, France.
  • Department of Hematology, Hôpital Avicenne, Bobigny, France.
  • Department of Hematology, Hôpital National d'Instruction des Armées Percy, Clamart, France.
  • Department of Clinical Hematology, Hôpital l'Archet, CHU de Nice, Nice, France.
  • Hematology Laboratory, CHU de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France.
  • Onco-Genetics Laboratory, Centre Henri Becquerel, Rouen, France.
  • Université de Toulouse, CHU de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Hematology Laboratory, Toulouse, France.
  • Department of Biostatistics, CHU d'Angers, Angers, France.
  • Department of Hematology, Institut Gustave Roussy, Villejuif, France.
  • Univ. Bordeaux, INSERM, BRIC, U1312, Service d'Hématologie Clinique et de Thérapie Cellulaire, CHU de Bordeaux, Bordeaux, France.

Abstract

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.

MeSH

Disease-Free Survival, Hematology, Anthracyclines