Midostaurin in combination with chemotherapy is most effective in patients with acute myeloid leukemia presenting with high FLT3-ITD allelic ratio who proceed to allogeneic stem cell transplantation while in first complete remission.
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Combined Modality Therapy
Female
Gene Duplication
Gene Frequency
Hematopoietic Stem Cell Transplantation
/ methods
Humans
Leukemia, Myeloid, Acute
/ diagnosis
Male
Middle Aged
Prognosis
Remission Induction
Retrospective Studies
Staurosporine
/ administration & dosage
Transplantation, Homologous
Treatment Outcome
fms-Like Tyrosine Kinase 3
/ genetics
acute myeloid leukemia
allogeneic stem cell transplantation
fms-like tyrosine kinase 3-internal tandem duplication
midostaurin
Journal
European journal of haematology
ISSN: 1600-0609
Titre abrégé: Eur J Haematol
Pays: England
ID NLM: 8703985
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
28
07
2020
revised:
08
09
2020
accepted:
08
09
2020
pubmed:
20
9
2020
medline:
29
7
2021
entrez:
19
9
2020
Statut:
ppublish
Résumé
Midostaurin, a multikinase and FLT3 inhibitor, is the first non-chemotherapy agent approved and widely adopted for the treatment of FLT3-ITD acute myeloid leukemia (AML). Yet, its role in improving survival of patients referred to allogeneic stem cell transplantation (allo-SCT) in first complete remission (CR1) needs to be defined. This multicenter study retrospectively evaluated the outcome of 119 FLT3-ITD AML patients [59 (49.6%) males and 60 females] intensively treated between 2015 and 2019 at five Israeli centers. In our cohort, allo-SCT in CR1 was widely implemented (47%) and patient stratification was based on the current allelic ratio (AR) cutoff of 0.5. Ninety-eight patients (82.3%) achieved CR1/CR with incomplete count recovery (CRi). Death during induction was reported in 7 (5.9%) patients. In multivariate analysis, midostaurin use and allo-SCT in CR1 were the most significant factors affecting overall survival (OS). Midostaurin incorporation in chemotherapy regimens significantly improved CR + CRi rates (P = .002), reduced relapse rates (P = .02), and was remarkably advantageous for high-AR patients (2-year OS 82%). In low-AR patients, the midostaurin effect was much less prominent. Our results demonstrate benefits of midostaurin incorporation in intensive chemotherapy regimens, particularly for high-AR AML patients to whom it should be offered along with allo-SCT in CR1.
Substances chimiques
FLT3 protein, human
EC 2.7.10.1
fms-Like Tyrosine Kinase 3
EC 2.7.10.1
Staurosporine
H88EPA0A3N
midostaurin
ID912S5VON
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
64-71Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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