Article Dans Une Revue NEJM Evidence Année : 2025

Intermediate-Dose Cytarabine as Postinduction AML Therapy

1 CRCI2NA - Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers
2 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
3 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
4 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
5 Service Hématologie - IUCT-Oncopole [CHU Toulouse]
6 CHU de Bordeaux Pellegrin [Bordeaux]
7 Inserm U1312 - BRIC - BoRdeaux Institute of onCology
8 AP-HP - Hopital Saint-Louis [AP-HP]
9 IRSL / U1342 - Institut de Recherche Saint Louis
10 CRCM - Centre de Recherche en Cancérologie de Marseille
11 Centre Hospitalier Universitaire [Rennes]
12 MOBIDIC - Microenvironment and B-cells: Immunopathology, Cell Differentiation, and Cancer
13 HCL - Hospices Civils de Lyon
14 CIRI - Centre International de Recherche en Infectiologie
15 Centre Esquirol [CHU Caen]
16 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
17 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
18 CIC 1402 - CIC de Poitiers – Centre d'investigation clinique de Poitiers (CIC 1402)
19 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
20 CHELTER - Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias
21 ICANS - Institut de Cancérologie de Strasbourg Europe
22 CHU Limoges
23 CHU Pitié-Salpêtrière [AP-HP]
24 CANTHER - Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
25 ALFA-CR - Acute Leukemia French Association-Clinical research
26 FILO - French Innovative Leukemia Organization
27 SFGM-TC - Société Francophone de Greffe de Moëlle et de Thérapie Cellulaire = French-speaking Society for Bone Marrow Transplantation and Cell Therapy
28 Hôpital Avicenne [AP-HP]
29 Irset - Institut de recherche en santé, environnement et travail
Sylvain Chantepie
Pascal Turlure
  • Fonction : Auteur
Claude Gardin
  • Fonction : Auteur
  • PersonId : 1071846

Résumé

Background: We conducted a randomized controlled trial to compare intermediate doses (IDAC) with high doses of cytarabine (HDAC) as postinduction therapy in patients 18 to 60 years of age with newly diagnosed acute myeloid leukemia (AML). The main objectives were to evaluate noninferiority in overall survival (OS) after IDAC and safety.
Methods: Patients 18 to 60 years of age with newly diagnosed AML, except those with core-binding factor, acute promyelocytic, Philadelphia chromosome-positive, or post-myeloproliferative neoplasm AML, were eligible. After the induction course, we randomly assigned patients to either IDAC (1500 mg/m2/12 hours) or HDAC (3000 mg/m2/12 hours). Patients with intermediate- and adverse-risk AML were eligible for allogeneic hematopoietic stem cell transplantation (HSCT) in first remission. The primary end point was OS in a predefined per-protocol analysis population. The primary analyses were performed in 1132 randomly assigned patients, with a noninferiority outcome adjusted on the European Leukemia Net (ELN) 2022 risk group, the use of induction anthracycline, the response to induction, and HSCT as a function of time following treatment.
Results: At 5 years, OS was estimated at 59.3% (95% confidence interval [CI], 55.0 to 63.3) in the IDAC group versus 57.5% (95% CI, 53.3 to 61.5) in the HDAC group (adjusted hazard ratio, 0.96; 95% CI, 0.80 to 1.15; noninferiority test, P=0.0042). A preplanned analysis was unable to detect any interaction between IDAC or HDAC treatment effect and patient subgroups, including those defined by the ELN 2022 risk group or response to induction prior to random assignment. In addition, the severity of chemotherapy-induced myelosuppression and the incidence of related adverse events were lower after IDAC.
Conclusions: Our trial shows noninferior outcomes in patients 18 to 60 years of age with newly diagnosed AML treated with low- versus high-dose cytarabine; this occurred with similar or lower toxicities.
(Funded by the Regional Clinical Research Office, Angers and others; EudraCT number, 2014-000699-24; ClinicalTrials.gov number, NCT02416388).

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Dates et versions

hal-05162195 , version 1 (15-07-2025)

Identifiants

Citer

Mathilde Hunault-Berger, Cécile Pautas, Sarah Bertoli, Pierre-Yves Dumas, Emmanuel Raffoux, et al.. Intermediate-Dose Cytarabine as Postinduction AML Therapy. NEJM Evidence, 2025, 4 (7), pp.EVIDoa2400326. ⟨10.1056/evidoa2400326⟩. ⟨hal-05162195⟩
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