Long-term follow-up of lower dose dasatinib (50 mg daily) as frontline therapy in newly diagnosed chronic-phase chronic myeloid leukemia.
Adult
Aged
Aged, 80 and over
Bridged Bicyclo Compounds, Heterocyclic
/ administration & dosage
Dasatinib
/ administration & dosage
Disease-Free Survival
Dose-Response Relationship, Drug
Female
Follow-Up Studies
Fusion Proteins, bcr-abl
/ antagonists & inhibitors
Humans
Imatinib Mesylate
/ administration & dosage
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/ drug therapy
Leukemia, Myeloid, Chronic-Phase
/ drug therapy
Male
Middle Aged
Protein Kinase Inhibitors
/ administration & dosage
Sulfonamides
/ administration & dosage
Treatment Outcome
chronic myeloid leukemia
complete cytogenetic response
dasatinib
major molecular response
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 01 2020
01 01 2020
Historique:
received:
31
05
2019
revised:
30
07
2019
accepted:
05
08
2019
pubmed:
26
9
2019
medline:
3
7
2020
entrez:
26
9
2019
Statut:
ppublish
Résumé
Dasatinib, a potent Bcr-Abl tyrosine kinase inhibitor, is approved for the treatment of chronic-phase chronic myeloid leukemia (CML-CP) in the frontline and salvage settings. Notable side effects include pleural effusions and myelosuppression. Dasatinib at 50 mg daily has previously been reported to be active and better tolerated than the approved 100-mg daily dose. The aim of this study was to update the long-term follow-up results of dasatinib at 50 mg daily as frontline therapy for CML-CP. Eighty-three patients with newly diagnosed CML-CP received dasatinib at 50 mg daily. Eligibility and response criteria were standards used in previous protocols. After a minimum follow-up of 12 months, 81 patients were evaluable. Two patients came off the study in less than 3 months. The rates of BCR-ABL1 transcript levels (International Standard) at ≤10% and ≤1% at 3 months were 96% and 77%, respectively. The cumulative rates for a complete cytogenetic response by 6 and 12 months were 77% and 95%, respectively. The cumulative rates for a major molecular response, a molecular response with a 4.0-log reduction, and a molecular response with a 4.5-log reduction by 12 months were 81%, 55%, and 49%, respectively. Twenty-one patients (25%) had treatment interruptions for a median of 13 days (range, 4-64 days). Five patients (6%) developed pleural effusions; 4 of these patients (80%) required a dose reduction. Two patients (2%) failed to achieve any cytogenetic or molecular response and were taken off the study. At a median follow-up of 24 months, none of the patients had disease transformation to an accelerated or blastic phase. The 2-year event-free and overall survival rates were 100%. These updated results continue to support 50 mg of dasatinib daily as an effective and safe dose for early CML-CP.
Sections du résumé
BACKGROUND
Dasatinib, a potent Bcr-Abl tyrosine kinase inhibitor, is approved for the treatment of chronic-phase chronic myeloid leukemia (CML-CP) in the frontline and salvage settings. Notable side effects include pleural effusions and myelosuppression. Dasatinib at 50 mg daily has previously been reported to be active and better tolerated than the approved 100-mg daily dose. The aim of this study was to update the long-term follow-up results of dasatinib at 50 mg daily as frontline therapy for CML-CP.
METHODS
Eighty-three patients with newly diagnosed CML-CP received dasatinib at 50 mg daily. Eligibility and response criteria were standards used in previous protocols.
RESULTS
After a minimum follow-up of 12 months, 81 patients were evaluable. Two patients came off the study in less than 3 months. The rates of BCR-ABL1 transcript levels (International Standard) at ≤10% and ≤1% at 3 months were 96% and 77%, respectively. The cumulative rates for a complete cytogenetic response by 6 and 12 months were 77% and 95%, respectively. The cumulative rates for a major molecular response, a molecular response with a 4.0-log reduction, and a molecular response with a 4.5-log reduction by 12 months were 81%, 55%, and 49%, respectively. Twenty-one patients (25%) had treatment interruptions for a median of 13 days (range, 4-64 days). Five patients (6%) developed pleural effusions; 4 of these patients (80%) required a dose reduction. Two patients (2%) failed to achieve any cytogenetic or molecular response and were taken off the study. At a median follow-up of 24 months, none of the patients had disease transformation to an accelerated or blastic phase. The 2-year event-free and overall survival rates were 100%.
CONCLUSIONS
These updated results continue to support 50 mg of dasatinib daily as an effective and safe dose for early CML-CP.
Identifiants
pubmed: 31553487
doi: 10.1002/cncr.32504
pmc: PMC8529949
mid: NIHMS1615545
doi:
Substances chimiques
Bridged Bicyclo Compounds, Heterocyclic
0
Protein Kinase Inhibitors
0
Sulfonamides
0
Imatinib Mesylate
8A1O1M485B
Fusion Proteins, bcr-abl
EC 2.7.10.2
venetoclax
N54AIC43PW
Dasatinib
RBZ1571X5H
Banques de données
ClinicalTrials.gov
['NCT02689440']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
67-75Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA100632
Pays : United States
Organisme : NIH HHS
ID : P30 CA016672
Pays : United States
Informations de copyright
© 2019 American Cancer Society.
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