Imatinib plasma levels in patients with chronic myeloid leukaemia under routine clinical practice conditions

Abstract

Introduction The addition of imatinib to the therapeutic arsenal for chronic myeloid leukaemia (CML) has changed the natural course of the disease, in such a way that it is now considered a chronic pathology. However, to achieve therapeutic success, it is necessary to reach adequate plasma concentrations to ensure efficacy and safety. In this study, we aimed to evaluate the plasma concentration of imatinib, analysing its influence on effectiveness and safety in patients with CML. Methods We performed a descriptive, multicentre study in which imatinib plasma levels from patients diagnosed with CML between 2019–2020 were analysed. An optimal therapeutic range of 750–1500 ng/mL was established for the stratification of patients, according to their minimum plasma concentrations measured at steady state (Cssmin). Results A total of 28 patients were included, of whom only 39.3% (n = 11) showed Cssmin within the therapeutic range. 100% of patients with Cssmin >750 ng/mL achieved an optimal molecular response, while only 50% of patients with Cssmin <750 ng/mL achieved an optimal molecular response ( p = 0.0004). The toxicity rate was 36.4% for patients with Cssmin >1500 ng/mL and 5.9% for those with Cssmin <1500 ng/mL ( p = 0.039). Conclusions This study aimed to describe the correlation between the toxicity and effectiveness of imatinib according to its Cssmin in routine clinical practice conditions. Based on our findings, it would be certainly justified to monitor patient plasma concentrations of imatinib on a daily routine basis in our hospitals.

Imatinib plasma levels in patients with gastrointestinal stromal tumour under routine clinical practice conditions

“…[14][15][16][17][18] Our research team has successfully shown in a previous study, the importance of monitoring imatinib Cssmin in CML in routine clinical practice, where we found that more than half of these individuals have plasma levels outside the therapeutic range, and a correlation between imatinib Cssmin, optimal molecular response rate and tolerance was determined. 18 Given the relevance of this issue, a series of guidelines have already been defined for personalising the therapy of various antineoplastic drugs based on their pharmacokinetic monitoring. [14][15][16][17] In the specific case of certain TKIs, such as imatinib, sunitinib and pazopanib, it is known that the optimisation of their dosage through this strategy increases the percentage of patients with adequate drug levels from 38% up to 64% 19 In conclusion, given the findings presented in this study, monitoring plasma levels of imatinib is a valuable strategy for optimising imatinib treatment and improving health outcomes in patients with GIST With this study, we wanted to show, under conditions of routine clinical practice, the correlation between the safety and effectiveness of imatinib and its plasma levels, which justifies the implementation of this pharmacokinetic monitoring in our hospitals.…”

“…17 Furthermore, the vast majority of oral antineoplastics have an exposure response and safety relationship, making a specific pharmacokinetic parameter such as Cssmin an excellent biomarker for dose individualisation. 14–18 Our research team has successfully shown in a previous study, the importance of monitoring imatinib Cssmin in CML in routine clinical practice, where we found that more than half of these individuals have plasma levels outside the therapeutic range, and a correlation between imatinib Cssmin, optimal molecular response rate and tolerance was determined. 18 Given the relevance of this issue, a series of guidelines have already been defined for personalising the therapy of various antineoplastic drugs based on their pharmacokinetic monitoring.…”

“…14–18 Our research team has successfully shown in a previous study, the importance of monitoring imatinib Cssmin in CML in routine clinical practice, where we found that more than half of these individuals have plasma levels outside the therapeutic range, and a correlation between imatinib Cssmin, optimal molecular response rate and tolerance was determined. 18 Given the relevance of this issue, a series of guidelines have already been defined for personalising the therapy of various antineoplastic drugs based on their pharmacokinetic monitoring. 14–17 In the specific case of certain TKIs, such as imatinib, sunitinib and pazopanib, it is known that the optimisation of their dosage through this strategy increases the percentage of patients with adequate drug levels from 38% up to 64% 19…”