Drug monitoring of imatinib levels in patients undergoing therapy for chronic myeloid leukaemia: comparing plasma levels of responders and non-responders

Abstract

Plasma levels of imatinib were correlated with response to the therapy, so routine monitoring of the therapeutic levels of the drug should be carried out specifically in treatment-resistant cases for determining dose escalation.

Imatinib plasma trough concentration and its correlation with characteristics and response in Chinese CML patients

“…Picard et al [9] concluded that imatinib plasma trough concentrations were correlated with both cytogenetic and molecular responses to standard-dose imatinib in CML, and the plasma threshold for C mins was set at 1002 ng/mL because it provided the best discrimination potential for achieving MMR. This conclusion was supported by other studies [10,11] . The inability to find a significant difference between patients in the CMR group and the no-CMR group is probably due to the fact that all of our patients had exceeded the plasma threshold of 1002 ng/mL, and this can in part explain why the patients treated with 600 mg imatinib daily didn't have significantly higher C mins than patients treated with 400 mg daily (P=0.267).…”

“…A subanalysis of the IRIS trial indicated that patients with high imatinib exposure had better rates of CCyR and MMR [10] . Singh et al [11] also reported that the mean C mins of imatinib responders were significantly higher than those of non-responders. However, it was also reported that there was no correlation between mean C mins and CCyR or MMR [12] .…”

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

“…Several other studies have also found that patients with better treatment outcomes also had higher C min values 23, 24…”

HPLC–MS method for the simultaneous quantification of the antileukemia drugs imatinib, dasatinib and nilotinib in human peripheral blood mononuclear cell (PBMC)

“…TDM, recently, has become an essential tool for the management of CML patients, particularly for patients taking imatinib [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39], which efficacy threshold in terms of plasma concentrations is clearly defined. In order to manage primary or acquired resistance to imatinib, clinical studies using dasatinib or nilotinib as second line therapy or combination of therapies with different TKIs, in sequential or simultaneous administration, are currently under evaluation [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. Sub-inhibitory intracellular drug concentrations, probably, and sequential treatment with multiple tyrosine kinase inhibitors promote the selection of BCR-ABL kinase domain mutations in CML patients [51][52].…”

“…Measurement of antileukemia drugs plasma concentrations reached by treated patients, then, can be useful to monitor CML patients over time, leading the evaluation of patient adherence to daily oral therapy, potential drug-drug interactions, treatment efficacy, and severe drug-related adverse events [20][21].…”