Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: a subanalysis from the RATIFY trial.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
13 10 2020
13 10 2020
Historique:
received:
29
07
2020
accepted:
21
08
2020
entrez:
13
10
2020
pubmed:
14
10
2020
medline:
15
5
2021
Statut:
ppublish
Résumé
The results from the RATIFY trial (ClinicalTrials.gov: NCT00651261; CALGB 10603) showed that midostaurin combined with standard chemotherapy significantly improved outcomes in patients with FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML), compared with placebo. In this post hoc subgroup analysis from the trial, we evaluated the impact of midostaurin in 163 patients with FLT3-tyrosine kinase domain (TKD) mutations. At a median follow-up of 60.7 months (95% CI, 55.0-70.8), the 5-year event-free survival (EFS) rate was significantly higher in patients treated with midostaurin than in those treated with placebo (45.2% vs 30.1%; P = .044). A trend toward improved disease-free survival was also observed with midostaurin (67.3% vs 53.4%; P = .089), whereas overall survival (OS) was similar in the 2 groups. Patients with AML and NPM1mut/FLT3-TKDmut or core binding factor (CBF)-rearranged/FLT3-TKDmut genotypes had significantly prolonged OS with or without censoring at hematopoietic cell transplantation (HCT), compared with NPM1WT/CBF-negative AMLs. The multivariable model for OS and EFS adjusted for allogeneic HCT in first complete remission as a time-dependent covariable, revealed NPM1 mutations and CBF rearrangements as significant favorable factors. These data show that NPM1 mutations or CBF rearrangements identify favorable prognostic groups in patients with FLT3-TKD AMLs, independent of other factors, also in the context of midostaurin treatment.
Identifiants
pubmed: 33049054
pii: S2473-9529(20)31228-3
doi: 10.1182/bloodadvances.2020002904
pmc: PMC7556122
doi:
Substances chimiques
NPM1 protein, human
0
Nucleophosmin
117896-08-9
FLT3 protein, human
EC 2.7.10.1
fms-Like Tyrosine Kinase 3
EC 2.7.10.1
Staurosporine
H88EPA0A3N
midostaurin
ID912S5VON
Banques de données
ClinicalTrials.gov
['NCT00651261']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4945-4954Subventions
Organisme : NCI NIH HHS
ID : UG1 CA233290
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA206963
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180821
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233180
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233338
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA196171
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180867
Pays : United States
Informations de copyright
© 2020 by The American Society of Hematology.
Références
Clin Lymphoma Myeloma Leuk. 2018 Dec;18(12):e545-e550
pubmed: 30082225
N Engl J Med. 2016 Feb 4;374(5):422-33
pubmed: 26789727
Blood. 2019 Nov 7;134(19):1608-1618
pubmed: 31554635
Blood. 2008 Jul 15;112(2):444-5; author reply 445
pubmed: 18606888
J Mol Diagn. 2003 May;5(2):96-102
pubmed: 12707374
Blood. 2002 Dec 15;100(13):4372-80
pubmed: 12393388
N Engl J Med. 2015 Sep 17;373(12):1136-52
pubmed: 26376137
Blood. 2006 May 15;107(10):4011-20
pubmed: 16455956
PLoS One. 2014 Mar 07;9(3):e89560
pubmed: 24608088
Haematologica. 2016 Mar;101(3):328-35
pubmed: 26635039
Blood. 2020 Jan 30;135(5):371-380
pubmed: 31826241
Blood. 2001 Sep 15;98(6):1752-9
pubmed: 11535508
J Natl Compr Canc Netw. 2019 Jun 1;17(6):721-749
pubmed: 31200351
Blood. 2008 Feb 1;111(3):1552-9
pubmed: 17940205
Blood. 2019 Feb 21;133(8):840-851
pubmed: 30563875
Blood Adv. 2017 Aug 17;1(19):1546-1550
pubmed: 29296796
Blood. 2008 Mar 1;111(5):2527-37
pubmed: 17965322
N Engl J Med. 2016 Jun 9;374(23):2209-2221
pubmed: 27276561
Blood. 2007 Aug 15;110(4):1262-70
pubmed: 17456725
N Engl J Med. 2008 May 1;358(18):1909-18
pubmed: 18450602
Leukemia. 2005 Aug;19(8):1479-82
pubmed: 15973451
Blood. 2012 Oct 4;120(14):2826-35
pubmed: 22875911
Leukemia. 2005 Aug;19(8):1345-9
pubmed: 15959528
Blood. 2017 Jan 26;129(4):424-447
pubmed: 27895058
Blood. 2009 Sep 17;114(12):2386-92
pubmed: 19602710
J Clin Oncol. 2011 Jul 1;29(19):2709-16
pubmed: 21555683
N Engl J Med. 2005 Jan 20;352(3):254-66
pubmed: 15659725
Blood. 2002 Jun 15;99(12):4326-35
pubmed: 12036858
N Engl J Med. 2017 Aug 3;377(5):454-464
pubmed: 28644114