Drug design, development and therapy · 2025
Dasatinib Dose Optimization Based on Therapeutic Drug Monitoring in Patients with Chronic-Phase Chronic Myeloid Leukemia.
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Cheng Fang, Cui Zheng, Li Qiang, Wang Liu, Zhang Yu, Li Weiming
Аннотация
BACKGROUND: Although a dosage decrease regimen for chronic phase chronic myeloid leukemia (CML-CP) has been suggested, there is a marked lack of guidance on individualizing medication dosages for patients.
METHODS: Our aim was to explore the application of therapeutic drug monitoring (TDM) as a strategy for optimizing dasatinib dosage in patients with CML-CP.
RESULTS: It was observed that patients administered a dosage of 100 mg exhibited significantly higher concentrations than those given 50 mg, with no marked difference in concentration between branded and generic drugs. Further analysis unveiled a robust correlation between peak concentration (Cmax) and clinical response (major molecular response (MMR): 103.8 ± 54.0 ng/mL versus 48.6 ± 13.9 ng/mL, P < 0.001; deep molecular response (DMR): 112.7 ± 57.6 ng/mL versus 66.2 ± 36.1 ng/mL, P = 0.001). Patients with a Cmax >51.85ng/mL were more likely to achieve MMR, while those with a Cmax surpassing 112.5 ng/mL had a higher probability of attaining DMR. We successfully implemented dasatinib dose reduction based on concentrations without loss of DMR in 22 patients undergoing first-line therapy. Moreover, trough concentrations (Cmin) >2.48 ng/mL were closely associated with the onset of pleural effusion. Older patients demonstrated higher Cmin and Cmax, irrespective of whether they were on a 50 mg or 100 mg dosage regimen.
CONCLUSION: TDM-based dose optimization could lead to beneficial clinical outcomes for patients with CML-CP. Furthermore, in terms of blood drug concentration, our findings supply additional evidence supporting the first-line treatment regimen of 50 mg daily.
METHODS: Our aim was to explore the application of therapeutic drug monitoring (TDM) as a strategy for optimizing dasatinib dosage in patients with CML-CP.
RESULTS: It was observed that patients administered a dosage of 100 mg exhibited significantly higher concentrations than those given 50 mg, with no marked difference in concentration between branded and generic drugs. Further analysis unveiled a robust correlation between peak concentration (Cmax) and clinical response (major molecular response (MMR): 103.8 ± 54.0 ng/mL versus 48.6 ± 13.9 ng/mL, P < 0.001; deep molecular response (DMR): 112.7 ± 57.6 ng/mL versus 66.2 ± 36.1 ng/mL, P = 0.001). Patients with a Cmax >51.85ng/mL were more likely to achieve MMR, while those with a Cmax surpassing 112.5 ng/mL had a higher probability of attaining DMR. We successfully implemented dasatinib dose reduction based on concentrations without loss of DMR in 22 patients undergoing first-line therapy. Moreover, trough concentrations (Cmin) >2.48 ng/mL were closely associated with the onset of pleural effusion. Older patients demonstrated higher Cmin and Cmax, irrespective of whether they were on a 50 mg or 100 mg dosage regimen.
CONCLUSION: TDM-based dose optimization could lead to beneficial clinical outcomes for patients with CML-CP. Furthermore, in terms of blood drug concentration, our findings supply additional evidence supporting the first-line treatment regimen of 50 mg daily.