title: Dasatinib in high-risk core binding factor acute myeloid leukemia in first complete remission: a French Acute Myeloid Leukemia Intergroup trial.
abstract: Core-binding factor acute myeloid leukemia is a favorable acute myeloid leukemia subset cytogenetically defined by t(8;21) or inv(16)/t(16;16) rearrangements, disrupting RUNX1 (previously CBFA/AML1) or CBFB transcription factor functions. The receptor tyrosine kinase KIT is expressed in the vast majority of these acute myeloid leukemias and frequent activating KIT gene mutations have been associated with a higher risk of relapse. This phase II study aimed to evaluate dasatinib as maintenance therapy in patients with core-binding factor acute myeloid leukemia in first hematologic complete remission, but at higher risk of relapse due to molecular disease persistence or recurrence. A total of 26 patients aged 18-60 years old previously included in the CBF-2006 trial were eligible to receive dasatinib 140 mg daily if they had a poor initial molecular response (n=18) or a molecular recurrence (n=8). The tolerance of dasatinib as maintenance therapy was satisfactory. The 2-year disease-free survival in this high-risk population of patients was 25.7%. All but one patient with molecular recurrence presented subsequent hematologic relapse. Patients with slow initial molecular response had a similar disease-free survival when treated with dasatinib (40.2% at 2 years) or without any maintenance (50.0% at 2 years). The disappearance of KIT gene mutations at relapse suggests that clonal devolution may in part explain the absence of efficacy observed with single-agent dasatinib in these patients (n. EudraCT: 2006-006555-12).
authors.affiliation: Service d'Hématologie Adulte, Hôpital Saint-Louis, Paris EA-3518, Université Paris 7 nicolas.boissel@sls.aphp.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Boissel
authors.affiliation: Laboratoire d'hématologie, Centre de Biologie-Pathologie, CHRU de Lille Equipe 3 INSERM U837, JPARC Lille.
authors.forename: Aline
authors.initials: A
authors.lastname: Renneville
authors.affiliation: Service d'Hématologie, Hôpital Haut-Lévèque, Bordeaux.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Leguay
authors.affiliation: Laboratoire Central d'Hématologie, CHU de Reims - Hôpital Robert Debré
authors.forename: Pascale Cornillet
authors.initials: PC
authors.lastname: Lefebvre
authors.affiliation: Service d'Hématologie, CHU Purpan, Toulouse.
authors.forename: Christian
authors.initials: C
authors.lastname: Recher
authors.affiliation: Service des Maladies du Sang, INSERM U892/CNRS 6299, CHU Angers.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Lecerf
authors.affiliation: Laboratoire d'Hématologie, CHU Purpan, Toulouse.
authors.forename: Eric
authors.initials: E
authors.lastname: Delabesse
authors.affiliation: Service des Maladies du Sang, CHU de Lille.
authors.forename: Céline
authors.initials: C
authors.lastname: Berthon
authors.affiliation: Laboratoire d'Hématologie, CHU Angers.
authors.forename: Odile
authors.initials: O
authors.lastname: Blanchet
authors.affiliation: Service d'Hématologie, Institut Paoli Calmettes, Marseille.
authors.forename: Thomas
authors.initials: T
authors.lastname: Prebet
authors.affiliation: Service d'Hématologie, CHU Henri Mondor, Créteil.
authors.forename: Cécile
authors.initials: C
authors.lastname: Pautas
authors.affiliation: Service d'Hématologie, CHU de Nantes.
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
authors.affiliation: Service d'Hématologie, Centre de Lutte Contre le Cancer, Rouen.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Leprêtre
authors.affiliation: Service d'Hématologie, CHU Dupuytren, Limoges.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Girault
authors.affiliation: Service d'Hématologie Adulte, Hôpitaux de Brabois, Nancy.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bonmati
authors.affiliation: Service d'Hématologie, CHU de Clermont Ferrand.
authors.forename: Romain
authors.initials: R
authors.lastname: Guièze
authors.affiliation: Service d'Hématologie, CHU de Reims - Hôpital Robert Debré
authors.forename: Chantal
authors.initials: C
authors.lastname: Himberlin
authors.affiliation: Service d'Hématologie, CHU de Poitiers.
authors.forename: Edouard
authors.initials: E
authors.lastname: Randriamalala
authors.affiliation: Laboratoire d'hématologie, Centre de Biologie-Pathologie, CHRU de Lille Equipe 3 INSERM U837, JPARC Lille.
authors.forename: Claude
authors.initials: C
authors.lastname: Preudhomme
authors.affiliation: Hématologie Clinique et Oncologie Médicale, CHU de Nîmes, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Jourdan
authors.affiliation: Service d'Hématologie Adulte, Hôpital Saint-Louis, Paris EA-3518, Université Paris 7.
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.affiliation: Service des Maladies du Sang, INSERM U892/CNRS 6299, CHU Angers.
authors.forename: Norbert
authors.initials: N
authors.lastname: Ifrah
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D050660:Core Binding Factors; D000069439:Dasatinib / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012074:Remission Induction / Q000379:methods; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D050660:Core Binding Factors; D000069439:Dasatinib