Impact of the type of tyrosine kinase inhibitor (imatinib or dasatinib) used before allo-HCT on outcome of patients with Philadelphia-positive acute lymphoblastic leukemia. A study on behalf of the Acute Leukemia Working Party of the EBMT. - Université de Lille
Article Dans Une Revue Transplantation and Cellular Therapy Année : 2024

Impact of the type of tyrosine kinase inhibitor (imatinib or dasatinib) used before allo-HCT on outcome of patients with Philadelphia-positive acute lymphoblastic leukemia. A study on behalf of the Acute Leukemia Working Party of the EBMT.

Sebastian Giebel
  • Fonction : Auteur
Zinaida Peric
  • Fonction : Auteur
Jakob Passweg
  • Fonction : Auteur
Urpu Salmenniemi
  • Fonction : Auteur
Péter Reményi
  • Fonction : Auteur
Stephan Mielke
  • Fonction : Auteur
Tobias Gedde-Dahl
  • Fonction : Auteur
Jan J. Cornelissen
  • Fonction : Auteur
Gesine Bug
  • Fonction : Auteur
Ali Bazarbachi
  • Fonction : Auteur
Arnon Nagler
  • Fonction : Auteur
Fabio Ciceri
  • Fonction : Auteur

Résumé

The use of tyrosine kinase inhibitors (TKIs) during induction and consolidation, followed by allogeneic hematopoietic cell transplantation (allo-HCT), is a standard of care for patients with Philadelphia (Ph)-positive acute lymphoblastic leukemia (ALL). The goal of this study was to compare results of allo-HCT according to the type of TKI used pre-transplant, either imatinib, dasatinib or both. This was a retrospective, registry-based analysis including adult patients with Ph-positive ALL treated with allo-HCT between years 2010-2022. The analysis included 606 patients pre-treated with imatinib, 163 with dasatinib and 94 with both imatinib and dasatinib. Allo-HCTs were performed in first complete remission from either unrelated (56%), matched sibling (36%) or haploidentical donors (8%). Relapse incidence at 2 years was 26% in the imatinib group and 21% in the dasatinib group and 19% in the imatinib + dasatinib group (P = .06) while non-relapse mortality was 19%, 15%, and 23%, respectively (P = .37). No significant differences were found for leukemia-free survival (55% vs. 63% vs. 58%, P = .11) and overall survival (72% vs. 76% vs. 65%, P = .32). The incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD was comparable across study groups, while the incidence of grade 3-4 acute GVHD was significantly increased for patients pre-treated with dasatinib alone (20%) than in the imatinib group (10%) or imatinib + dasatinib group (13%) (P = .002). On multivariate analysis a chance of GVHD and relapse-free survival (GRFS) was significantly decreased while the risk of grade 3-4 acute GVHD was increased for the dasatinib compared to imatinib group (hazard ratio, HR = 1.27, P = .048 and HR = 2.26, P = .0009, respectively). This study provides no evidence for the advantage of one TKI over another in terms of LFS and OS. However, the use of dasatinib is associated with increased risk of severe acute GVHD and decreased GRFS.
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Dates et versions

hal-04689053 , version 1 (05-09-2024)

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Sebastian Giebel, Myriam Labopin, Zinaida Peric, Jakob Passweg, Didier Blaise, et al.. Impact of the type of tyrosine kinase inhibitor (imatinib or dasatinib) used before allo-HCT on outcome of patients with Philadelphia-positive acute lymphoblastic leukemia. A study on behalf of the Acute Leukemia Working Party of the EBMT.. Transplantation and Cellular Therapy, 2024, Transplantation and Cellular Therapy, ⟨10.1016/j.jtct.2024.07.016⟩. ⟨hal-04689053⟩
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