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.

Reply to “Plasma imatinib trough levels for predicting efficacy and toxicity in patients with chronic myeloid leukemia in chronic phase: Still a matter of debate!”

“…The authors have no conflicts of interest to declare. Fang Cheng MD 1,2 Fang Zeng MD 1,2 Qiang Li PhD 1,2 Zheng Cui PhD 1,2 Yilin Chen MD 3 Weiming Li PhD 3 Yu Zhang PhD 1,2 1…”

Plasma imatinib trough levels for predicting efficacy and toxicity in patients with chronic myeloid leukemia in chronic phase: Still a matter of debate!

“…1 In patients with CML-CP, it was previously shown that imatinib concentrations could be associated with clinical responses. 2,3 Cheng et al 4 have demonstrated that, in addition to therapeutic efficacy, plasma imatinib trough levels are also associated with toxicities.…”

“…1 In patients with CML-CP, it was previously shown that imatinib concentrations could be associated with clinical responses. 2,3 Cheng et al 4 have demonstrated that, in addition to therapeutic efficacy, plasma imatinib trough levels are also associated with toxicities.Although this is a very informative study with very interesting findings, there are still some points that need to be further underlined:� The authors stated that they included patients with "good compliance"; however, they did not define what was accepted as good compliance. Previously, Marin and colleagues 5 clearly showed that patients with an imatinib adherence rate of >90% had significantly higher rates of major molecular response (MMR) and deep molecular response than those with an adherence rate of…”

“…� The median age of the defined cohort was 45 years, with the oldest patient being 55 years old. 4 This was most likely due to the exclusion of elderly patients concomitantly using drugs that might have affected the imatinib concentration. Although the median age of patients with chronic myeloid leukemia at diagnosis can be 40-50 years in some populations, 6 it is generally 57-60 years.…”

“…Thus, this information should have been shared. � Lastly, eight patients who experienced failure with imatinib switched to second-generation TKIs (2G-TKIs), but the number of patients who did not achieve MMR during imatinib therapy was 17 4 ; this, I guess, needs an explanation. In addition, as the authors showed, the mean imatinib trough concentration was significantly lower in those without MMR in comparison with cases achieving MMR.…”