Appropriate Starting Dose of Dasatinib Based on Analyses of Dose-Limiting Toxicities and Molecular Responses in Asian Patients With Chronic Myeloid Leukemia

Abstract

The fixed starting dosage of dasatinib 100 mg once daily may not be optimal for Asian patients with chronic myeloid leukemia in chronic phase (CP-CML). The dose-limiting toxicities (DLTs) and molecular responses (MRs) of dasatinib therapy were analyzed using clinical and demographic data obtained from patients with CP-CML at 17 hospitals in South Korea. Patients with a larger dasatinib dose adjusted for body weight (Dose/BW) experienced a higher rate of DLTs, whereas the magnitude of Dose/BW does not affect the rate of MR achievement. Therefore, the starting dosage may need to be reduced to 80 mg once daily in Asian patients with CP-CML, especially those with lighter BW. Background: Dasatinib is administered at a fixed starting dosage of 100 mg once daily regardless of patient-specific factors. However, such fixed dosing may not be optimal for the treatment of Asian patients with chronic myeloid leukemia in chronic phase (CP-CML). Patients and Methods: The dose-limiting toxicities (DLTs) and molecular responses (MRs) of dasatinib therapy were evaluated using clinical data obtained from 102 patients newly diagnosed with CP-CML at 17 hospitals in South Korea. Results: By 36 months after the initiation of a fixed dose regimen of dasatinib 100 mg once daily as the first-line therapy, 55.9% of patients experienced at least one type of DLT. The 3 most frequent DLTs were thrombocytopenia (45.5%), pericardial or pleural effusion (30.9%), and anemia (7.3%). Patients with higher dasatinib dose adjusted for body weight (Dose/BW) had a greater rate of DLT occurrence (logit [P] = 1.58 x [Dose/BW] - 2.27, P = .03). As median Dose/BW increased from 1.23 to 2.00 mg/kg, the rate of DLT occurrence increased from 43.5% to 66.7% (P = .03). However, Dose/BW did not affect the achievement rate of major MR (60.9% to 69.6%, P = .92). Conclusion: The starting dosage of dasatinib may need to be reduced (eg, 80 mg once daily or lower) for Asian patients with CP-CML, especially with lighter BW, to alleviate the risk of DLT occurrence without compromising the achievement of MR. (C) 2021 Elsevier Inc. All rights reserved.