Early dose reduction of dasatinib does not compromise clinical outcomes in patients with chronic myeloid leukemia: A comparative analysis of two prospective trials

Dong Yeop Shin, Sahee Park, Eunjung Jang, Jee Hyun Kong, Young Woong Won, Sukjoong Oh, Yunsuk Choi, Jeong A. Kim, Se Won Lee, Yeung Chul Mun, Hawk Kim, Sung Hyun Kim, Young Rok Do, Jae Yong Kwak, Hyeoung Joon Kim, Dae Young Zang, Sung Nam Lim, Won Sik Lee, Dong Wook Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Dasatinib is a potent second-generation tyrosine kinase inhibitor (TKI) used as a first-line treatment option for patients with chronic myeloid leukemia (CML). Currently, dose modification due to adverse events (AEs) is common in patients treated with dasatinib. This study compared the outcomes of two sequential prospective trials that enrolled patients with newly diagnosed chronic phase of CML (CP-CML) and initiated dasatinib at a starting dose of 100 mg daily. In the PCR-DEPTH study, CP-CML patients who started dasatinib 100 mg daily were enrolled and followed up, while in the DAS-CHANGE study, when patients achieved early molecular response with any grade of AEs were enrolled and treated with dasatinib 80 mg once daily. A total of 102 patients (PCR-DEPTH) and 90 patients (DAS-CHANGE) were compared. Although the median value of the relative dose intensity (RDI) of dasatinib was significantly higher in PCR-DEPTH than in DAS-CHANGE (99.6 % vs. 80.1 %, p <0.001), the MMR rate at 12months showed a trend toward superiority in DAS-CHANGE compared to PCR-DEPTH (77.1 % vs 65.2 %, p = 0.084). The frequencies of MR4.0 at 24 and 36 months were higher in DAS-CHANGE than in PCR-DEPTH (44.4 % vs 28.8 %, p = 0.052 and 63.6 % vs 40.3 %, p= 0.013, respectively). RDIs were not different according to the MMR, MR4.0 or MR4.5 in analyses using a pooled population. Our results suggest that early dose reduction of dasatinib does not compromise efficacy in patients achieving EMR at 3 months and could be an interventional strategy for improving long term outcomes.

Original languageEnglish
Article number107542
JournalLeukemia Research
Volume143
DOIs
StatePublished - Aug 2024

Bibliographical note

Publisher Copyright:
© 2024

Keywords

  • Chronic myeloid leukemia
  • Dasatinib
  • Dose modification
  • Molecular response

Fingerprint

Dive into the research topics of 'Early dose reduction of dasatinib does not compromise clinical outcomes in patients with chronic myeloid leukemia: A comparative analysis of two prospective trials'. Together they form a unique fingerprint.

Cite this