Low-Dose Dasatinib (50 mg Daily) Frontline Therapy in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: 5-Year Follow-Up Results.


Journal

Clinical lymphoma, myeloma & leukemia
ISSN: 2152-2669
Titre abrégé: Clin Lymphoma Myeloma Leuk
Pays: United States
ID NLM: 101525386

Informations de publication

Date de publication:
10 2023
Historique:
received: 05 04 2023
revised: 17 05 2023
accepted: 18 05 2023
medline: 25 9 2023
pubmed: 13 6 2023
entrez: 12 6 2023
Statut: ppublish

Résumé

Dasatinib is a BCR::ABL1 tyrosine kinase inhibitor approved as frontline therapy at a 100 mg daily for chronic myeloid leukemia in chronic phase (CML-CP). The use of a lower dose of dasatinib (50 mg daily) has demonstrated better tolerance and improved outcomes compared with the standard dose. Here, we report the updated results in a large cohort with a 5-year follow-up. Patients with newly diagnosed CML-CP were eligible. Entry and response-outcome criteria were standard. Dasatinib was given as 50 mg orally daily. Eighty-three patients were included. At 3 months, 78 (96%) patients achieved BCR::ABL1 transcripts (IS) ≤10%, and at 12 months, 65 (81%) patients achieved BCR::ABL1 transcript (IS) ≤0.1%. The cumulative incidence of complete cytogenetic, major molecular, and deep molecular responses at 5 years were 98%, 95%, and 82%, respectively. Rates of failures due to resistance (n = 4; 5%) and toxicity (n = 4; 5%) were low. The 5-year overall survival was 96% and event-free survival 90%. No transformations to accelerated or blastic phase were observed. Grade 3 to 4 pleural effusions developed in 2% of patients. Dasatinib 50 mg daily is an effective and safe treatment for newly diagnosed CML-CP.

Sections du résumé

BACKGROUND
Dasatinib is a BCR::ABL1 tyrosine kinase inhibitor approved as frontline therapy at a 100 mg daily for chronic myeloid leukemia in chronic phase (CML-CP). The use of a lower dose of dasatinib (50 mg daily) has demonstrated better tolerance and improved outcomes compared with the standard dose. Here, we report the updated results in a large cohort with a 5-year follow-up.
PATIENTS AND METHODS
Patients with newly diagnosed CML-CP were eligible. Entry and response-outcome criteria were standard. Dasatinib was given as 50 mg orally daily.
RESULTS
Eighty-three patients were included. At 3 months, 78 (96%) patients achieved BCR::ABL1 transcripts (IS) ≤10%, and at 12 months, 65 (81%) patients achieved BCR::ABL1 transcript (IS) ≤0.1%. The cumulative incidence of complete cytogenetic, major molecular, and deep molecular responses at 5 years were 98%, 95%, and 82%, respectively. Rates of failures due to resistance (n = 4; 5%) and toxicity (n = 4; 5%) were low. The 5-year overall survival was 96% and event-free survival 90%. No transformations to accelerated or blastic phase were observed. Grade 3 to 4 pleural effusions developed in 2% of patients.
CONCLUSION
Dasatinib 50 mg daily is an effective and safe treatment for newly diagnosed CML-CP.

Identifiants

pubmed: 37308342
pii: S2152-2650(23)00167-2
doi: 10.1016/j.clml.2023.05.009
pii:
doi:

Substances chimiques

Dasatinib RBZ1571X5H
Protein Kinase Inhibitors 0
Fusion Proteins, bcr-abl EC 2.7.10.2

Banques de données

ClinicalTrials.gov
['NCT02689440']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

742-748

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Auteurs

Georgina Gener-Ricos (G)

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.

Fadi G Haddad (FG)

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.

Koji Sasaki (K)

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.

Ghayas C Issa (GC)

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.

Jeffrey Skinner (J)

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.

Lucia Masarova (L)

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.

Gautam Borthakur (G)

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.

Yesid Alvarado (Y)

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.

Guillermo Garcia-Manero (G)

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.

Elias Jabbour (E)

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.

Hagop Kantarjian (H)

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: hkantarjian@mdanderson.org.

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Classifications MeSH