Dasatinib in high-risk core binding factor acute myeloid leukemia in first complete remission: a French Acute Myeloid Leukemia Intergroup trial

Nicolas Boissel 1, 2, * Aline Renneville 3, 4 Thibaut Leguay 5 Pascale Lefebvre 6 Christian Recher 7 Thibaud Lecerf 8, 9 Eric Delabesse 10 Céline Berthon 11 Odile Blanchet 12 Thomas Prebet 13 Cécile Pautas 14 Patrice Chevallier 15 Stéphane Leprêtre 16 Stéphane Girault 17 Caroline Bonmati 18 Romain Guièze 19 Chantal Himberlin 20 Edouard Randriamalala 21 Claude Preudhomme 3, 4 Eric Jourdan 22 Hervé Dombret 1, 2 Norbert Ifrah 8
* Corresponding author
1 Service d'hématologie-oncologie adultes
2 (EA_3518) - Recherche clinique appliquée à l'hématologie
3 Centre de Biologie et de Pathologie - Laboratoire d'Hématologie [CHRU Lille]
4 INSERM U837 - Equipe 3 - Facteurs de persistance des cellules leucémique -
U837 INSERM - IRCL - Institut pour la Recherche sur le Cancer de Lille
5 Service d’Hématologie [Hôpital Haut-Lévèque, CHU Bordeaux]
6 Laboratoire Central d'Hématologie [Hôpital Robert Debré, CHU Reims]
7 Service d’Hématologie [CHU Purpan, Toulouse]
8 CRCNA - Centre de Recherche en Cancérologie / Nantes - Angers
9 Service des maladies du sang [CHU Angers]
10 Laboratoire d'Hématologie [Purpan]
11 Service des Maladies du Sang [CHRU Lille]
12 Laboratoire d'Hématologie [CHU Angers]
13 Service d’Hématologie [Institut Paoli Calmettes, Marseille]
14 Service d'Hématologie Biologique
15 Service d'Hématologie [CHU Nantes]
16 Laboratoire d'hématologie [Rouen]
17 Service d'Hématologie biologique [CHU Limoges]
18 Service d’Hématologie Adulte [Hôpitaux de Brabois, CHU Nancy]
19 Service d’Hématologie [CHU de Clermont Ferrand]
20 Service d’Hématologie [Hôpital Robert Debré, CHU Reims]
21 Service d'Hématologie [CHU Poitiers]
22 Service d'Hématologie Clinique et Oncologie Médicale [CHU de Nîmes]
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).
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Nicolas Boissel, Aline Renneville, Thibaut Leguay, Pascale Lefebvre, Christian Recher, et al.. Dasatinib in high-risk core binding factor acute myeloid leukemia in first complete remission: a French Acute Myeloid Leukemia Intergroup trial. Haematologica, Ferrata Storti Foundation, 2015, 100 (6), pp.780 - 785. ⟨10.3324/haematol.2014.114884⟩. ⟨inserm-01820455⟩

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