Venetoclax combined with FLAG-IDA induction and consolidation in newly diagnosed acute myeloid leukemia.
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Bridged Bicyclo Compounds, Heterocyclic
/ adverse effects
Cytarabine
/ therapeutic use
Granulocyte Colony-Stimulating Factor
/ therapeutic use
Humans
Idarubicin
/ therapeutic use
Leukemia, Myeloid, Acute
/ diagnosis
Middle Aged
Prospective Studies
Remission Induction
Sulfonamides
/ adverse effects
Vidarabine
/ therapeutic use
Young Adult
Journal
American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
10
05
2022
received:
18
04
2022
accepted:
12
05
2022
pubmed:
19
5
2022
medline:
9
7
2022
entrez:
18
5
2022
Statut:
ppublish
Résumé
Multi-agent induction chemotherapy (IC) improves response rates in younger patients with acute myeloid leukemia (AML); however, relapse remains the principal cause of treatment failure. Improved induction regimens are needed. A prospective single-center phase Ib/II study evaluating fludarabine, cytarabine, G-CSF, and idarubicin combined with venetoclax (FLAG-IDA + VEN) in patients with newly diagnosed (ND) or relapsed/refractory AML. The primary efficacy endpoint was assessment of overall activity (overall response rate [ORR]: complete remission [CR] + CR with partial hematologic recovery [CRh] + CR with incomplete hematologic recovery [CRi] + morphologic leukemia free state + partial response). Secondary objectives included additional assessments of efficacy, overall survival (OS), and event-free survival (EFS). Results of the expanded ND cohort with additional follow-up are reported. Forty-five patients (median age: 44 years [range 20-65]) enrolled. ORR was 98% (N = 44/45; 95% credible interval 89.9%-99.7%). Eighty-nine percent (N = 40/45) of patients attained a composite CR (CRc + CRh + CRi) including 93% (N = 37/40) who were measurable residual disease (MRD) negative. Twenty-seven (60%) patients transitioned to allogeneic stem cell transplant (alloHSCT). Common non-hematologic adverse events included febrile neutropenia (44%; N = 20), pneumonia (22%, N = 10), bacteremia (18%, N = 8), and skin/soft tissue infections (44%, N = 20). After a median follow-up of 20 months, median EFS and OS were not reached. Estimated 24-month EFS and OS were 64% and 76%, respectively. FLAG-IDA + VEN is an active regimen in ND-AML capable of producing high MRD-negative remission rates and enabling transition to alloHSCT when appropriate in most patients. Toxicities were as expected with IC and were manageable. Estimated 24-month survival appears favorable compared to historical IC benchmarks.
Substances chimiques
Bridged Bicyclo Compounds, Heterocyclic
0
Sulfonamides
0
Cytarabine
04079A1RDZ
Granulocyte Colony-Stimulating Factor
143011-72-7
Vidarabine
FA2DM6879K
venetoclax
N54AIC43PW
Idarubicin
ZRP63D75JW
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1035-1043Subventions
Organisme : NCI NIH HHS
ID : R01 CA235622
Pays : United States
Informations de copyright
© 2022 Wiley Periodicals LLC.
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