Midostaurin reduces relapse in FLT3-mutant acute myeloid leukemia: the Alliance CALGB 10603/RATIFY trial.
Adolescent
Adult
Antineoplastic Agents
/ therapeutic use
Biomarkers, Tumor
/ genetics
Female
Follow-Up Studies
Humans
Leukemia, Myeloid, Acute
/ drug therapy
Male
Middle Aged
Mutation
Neoplasm Recurrence, Local
/ drug therapy
Prognosis
Prospective Studies
Staurosporine
/ analogs & derivatives
Survival Rate
Young Adult
fms-Like Tyrosine Kinase 3
/ genetics
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
27
09
2020
accepted:
01
02
2021
revised:
13
01
2021
pubmed:
4
3
2021
medline:
6
10
2021
entrez:
3
3
2021
Statut:
ppublish
Résumé
The prospective randomized, placebo-controlled CALGB 10603/RATIFY trial (Alliance) demonstrated a statistically significant overall survival benefit from the addition of midostaurin to standard frontline chemotherapy in a genotypically-defined subgroup of 717 patients with FLT3-mutant acute myeloid leukemia (AML). The risk of death was reduced by 22% on the midostaurin-containing arm. In this post hoc analysis, we analyzed the cumulative incidence of relapse (CIR) on this study and also evaluated the impact of 12 4-week cycles of maintenance therapy. CIR analyses treated relapses and AML deaths as events, deaths from other causes as competing risks, and survivors in remission were censored. CIR was improved on the midostaurin arm (HR = 0.71 (95% CI, 0.54-0.93); p = 0.01), both overall and within European LeukemiaNet 2017 risk classification subsets when post-transplant events were considered in the analysis as events. However, when transplantation was considered as a competing risk, there was overall no significant difference between the risks of relapse on the two randomized arms. Patients still in remission after consolidation with high-dose cytarabine entered the maintenance phase, continuing with either midostaurin or placebo. Analyses were inconclusive in quantifying the impact of the maintenance phase on the overall outcome. In summary, midostaurin reduces the CIR.
Identifiants
pubmed: 33654204
doi: 10.1038/s41375-021-01179-4
pii: 10.1038/s41375-021-01179-4
pmc: PMC8591906
mid: NIHMS1736300
doi:
Substances chimiques
Antineoplastic Agents
0
Biomarkers, Tumor
0
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
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2539-2551Subventions
Organisme : NCI NIH HHS
ID : U10 CA032291
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA077658
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180821
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180836
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA041287
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA196171
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180820
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180867
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180888
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233328
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233290
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233331
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180791
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180850
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA077651
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180863
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233180
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180882
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233338
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.
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