Imatinib dose optimization based on therapeutic drug monitoring in Chinese patients with chronic-phase chronic myeloid leukemia

Abstract

Background: Imatinib treatment often produces various adverse reactions in patients with chronic myeloid leukemia (CML), and increasing patients are pursuing dose optimization. In this study, the authors aimed to explore imatinib dose optimization based on therapeutic drug monitoring (TDM) in CML patients.

Methods: The relationship between imatinib concentration and clinical response and adverse reactions was evaluated, then the dose-reduction data in 110 Chinese CML patients was also explored.

Results: Patients with a major molecular response (MMR) had higher imatinib plasma concentration compared with those not achieving MMR (1473.70 ± 419.13 vs. 985.8 ± 213.32 ng/ml) when receiving 400 mg daily. Imatinib concentration >1000 ng/ml predicted improved event-free survival and failure-free survival. In addition, imatinib concentration was significantly correlated with leukopenia or neutropenia, diarrhea, edema, and rash. Patients receiving imatinib concentration >1685 ng/ml were more susceptible to diarrhea and those with levels >1575 ng/ml were more susceptible to periorbital and limb edema. Thirty-nine (35.5%) patients underwent low-dose therapy and seven (6.4%) patients received discontinuation therapy. Patients with a higher imatinib concentration were more likely to maintain MMR or deep molecular response after dose reduction. No significant difference in molecular relapse-free survival rate was observed between the low-dose and standard-dose groups over 1 year and 2 years. Furthermore, most adverse reactions significantly improved after dose reduction.

Conclusions: Imatinib concentration was closely associated with clinical response and adverse reactions, suggesting that dose optimization based on TDM might achieve beneficial clinical outcomes. Dose reduction based on TDM is feasible and safe for patients exhibiting optimal response, which could improve adverse reactions.

Keywords: adverse reactions; chronic myeloid leukemia; dose optimization; imatinib; therapeutic drug monitoring.