Sorafenib plus intensive chemotherapy improves survival in patients with newly diagnosed, FLT3-internal tandem duplication mutation-positive acute myeloid leukemia.
Acute Disease
Adult
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Cohort Studies
Combined Modality Therapy
Female
Hematopoietic Stem Cell Transplantation
/ methods
Humans
Induction Chemotherapy
/ methods
Kaplan-Meier Estimate
Leukemia, Myeloid
/ genetics
Male
Middle Aged
Mutation
Remission Induction
Sorafenib
/ administration & dosage
Staurosporine
/ administration & dosage
Tandem Repeat Sequences
/ genetics
Transplantation, Homologous
Young Adult
fms-Like Tyrosine Kinase 3
/ genetics
FLT3-internal tandem duplication (FLT3-ITD)
acute myeloid leukemia
allogeneic stem cell transplantation
induction chemotherapy
sorafenib
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 Nov 2019
01 Nov 2019
Historique:
received:
10
04
2019
revised:
14
05
2019
accepted:
20
05
2019
pubmed:
17
7
2019
medline:
27
5
2020
entrez:
17
7
2019
Statut:
ppublish
Résumé
The addition of midostaurin to induction chemotherapy improves survival in younger patients with newly diagnosed, FLT3-mutated acute myeloid leukemia (AML). Sorafenib is a potent multikinase inhibitor with efficacy when given as monotherapy. The authors investigated whether the addition of sorafenib to intensive induction chemotherapy improves outcomes in patients with FLT3-internal tandem duplication (ITD)-mutated AML. In total, 183 patients who were newly diagnosed with FLT3-ITD-mutated AML between February 2001 and December 2017 were identified. Of these, 79 patients (43%) underwent intensive chemotherapy with the addition of sorafenib, and 104 (57%) received intensive chemotherapy alone. Propensity score matching identified 42 patients in each cohort. The overall response rate was 98% in the sorafenib cohort and 83% in the intensive chemotherapy cohort (P = .057). The median follow-up was 54 months. The median event-free survival was 35 months in the sorafenib cohort and 8 months in the intensive chemotherapy cohort (P = .019), and the median overall survival was 42 and 13 months, respectively (P = .026). With censoring at the time of allogeneic stem cell transplantation, the median event-free survival was 31 and 8 months in the sorafenib and intensive therapy cohorts, respectively (P = .031), and the median overall survival was not reached and 10 months, respectively (P = .001). Multivariate Cox proportional hazards models confirmed that treatment with sorafenib was a favorable prognostic factor (P = .009; hazard ratio, 0.558; 95% CI, 0.360-0.865). The addition of sorafenib improves survival in patients with FLT3-ITD-mutated AML regardless of whether they undergo allogeneic stem cell transplantation.
Sections du résumé
BACKGROUND
BACKGROUND
The addition of midostaurin to induction chemotherapy improves survival in younger patients with newly diagnosed, FLT3-mutated acute myeloid leukemia (AML). Sorafenib is a potent multikinase inhibitor with efficacy when given as monotherapy. The authors investigated whether the addition of sorafenib to intensive induction chemotherapy improves outcomes in patients with FLT3-internal tandem duplication (ITD)-mutated AML.
METHODS
METHODS
In total, 183 patients who were newly diagnosed with FLT3-ITD-mutated AML between February 2001 and December 2017 were identified. Of these, 79 patients (43%) underwent intensive chemotherapy with the addition of sorafenib, and 104 (57%) received intensive chemotherapy alone. Propensity score matching identified 42 patients in each cohort.
RESULTS
RESULTS
The overall response rate was 98% in the sorafenib cohort and 83% in the intensive chemotherapy cohort (P = .057). The median follow-up was 54 months. The median event-free survival was 35 months in the sorafenib cohort and 8 months in the intensive chemotherapy cohort (P = .019), and the median overall survival was 42 and 13 months, respectively (P = .026). With censoring at the time of allogeneic stem cell transplantation, the median event-free survival was 31 and 8 months in the sorafenib and intensive therapy cohorts, respectively (P = .031), and the median overall survival was not reached and 10 months, respectively (P = .001). Multivariate Cox proportional hazards models confirmed that treatment with sorafenib was a favorable prognostic factor (P = .009; hazard ratio, 0.558; 95% CI, 0.360-0.865).
CONCLUSIONS
CONCLUSIONS
The addition of sorafenib improves survival in patients with FLT3-ITD-mutated AML regardless of whether they undergo allogeneic stem cell transplantation.
Substances chimiques
Sorafenib
9ZOQ3TZI87
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
Langues
eng
Sous-ensembles de citation
IM
Pagination
3755-3766Subventions
Organisme : Leukemia Texas
Informations de copyright
© 2019 American Cancer Society.
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