Low-Dose Dasatinib 50 mg/Day Versus Standard-Dose Dasatinib 100 mg/Day As Frontline Therapy in Chronic Myeloid Leukemia in Chronic Phase: A Propensity Score Analysis

Authors

Elias Jabbour
Koji Sasaki
Fadi G Haddad
Ghayas C Issa
Jeffrey Skinner
Sara Dellasala
Musa Yilmaz
Alessandra Ferrajoli
Prithviraj Bose
Philip Thompson
Yesid Alvarado
Nitin Jain
Guillermo Garcia-Manero
Koichi Takahashi
Gautam Borthakur
Naveen Pemmaraju
Sherry Pierce
Hagop Kantarjian

Publication Date

11-1-2022

Journal

American Journal of Hematology

Abstract

Low-dose dasatinib is safe and effective in patients with chronic myeloid leukemia in chronic phase (CML-CP). No randomized trials have compared the outcome with standard-dose dasatinib. This study aims to compare the outcome of patients with CML-CP treated with frontline dasatinib 50 versus 100 mg/day. We analyzed 233 patients with newly diagnosed CML-CP treated with low-dose dasatinib (N = 83) or standard-dose dasatinib (N = 150). Propensity score analysis with 1:1 matching was performed and identified 77 patients in each cohort without significant baseline differences. Response rates were reported as the cumulative incidences of complete cytogenetic response, major molecular response (MMR), molecular response (MR)4, and MR4.5. Failure-free survival (FFS), event-free survival (EFS), transformation-free survival (TFS), and overall survival (OS) were also compared. Patients on low-dose dasatinib with suboptimal response by European LeukemiaNet (ELN) 2013 criteria had the option to increase the dose to 100 mg/day. The overall median follow-up time was 60 months. The 3-year MMR rates were 92% and 84% for low-dose and standard-dose dasatinib, respectively (p = .23). Dasatinib 50 mg/day induced higher cumulative incidence of MR4 (77% vs. 66%; p = .04) and MR4.5 (77% vs. 62%; p = .02) at 3 years. The 4-year FFS, EFS and OS rates were 89% versus 77% (p = .04), 95% versus 92% (p = .06), and 97% versus 96% (p = .78) with low-dose and standard-dose dasatinib, respectively. The rate of any grade pleural effusion was 5% with dasatinib 50 mg/day compared to 21% with 100 mg/day. Dasatinib 50 mg/day is at least as effective as 100 mg/day with a better safety profile and drug exposure.

Keywords

Antineoplastic Agents, Dasatinib, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Chronic-Phase, Propensity Score, Protein Kinase Inhibitors, Treatment Outcome

DOI

10.1002/ajh.26689

PMID

36054032

PMCID

PMC11837974

PubMedCentral® Posted Date

2-19-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes