Toward Clinical Implementation of a Volumetric Absorptive Microsampling-Based Method for Dasatinib and Imatinib Therapeutic Drug Monitoring.

BACKGROUND

Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors may improve treatment outcomes and individualized therapy in patients with cancer. Compared with plasma, the standard TDM matrix, dried blood microsampling is associated with several advantages, including the collection of samples by the patients themselves in their home setting. This study aimed to compare dasatinib and imatinib concentrations in different blood-based matrices and to determine whether dried capillary blood collected via volumetric absorptive microsampling (VAMS) could be used as an alternative to perform TDM in patients with chronic myeloid leukemia.

METHODS

In addition to venous liquid whole blood, plasma, and VAMS samples (referred to as venous VAMS) prepared thereof, also fingerprick capillary VAMS samples were collected from patients receiving dasatinib or imatinib treatment by skilled personnel in a controlled environment. All samples were analyzed using validated liquid chromatography tandem mass spectrometry methods.

RESULTS

Fifty-three patients were included in the study: 33 were treated with dasatinib and 20 with imatinib. Although a bias between dasatinib and imatinib venous VAMS and liquid blood concentrations was observed, 94% and 95% of the samples, respectively, fulfilled the 20% difference acceptance criterion. Capillary and venous concentrations were interchangeable and independent of the collection time. Using venous blood-to-plasma ratios from a prior proof-of-concept study, the VAMS results for imatinib, but not dasatinib, could reliably be converted into plasma concentrations.

CONCLUSIONS

Through a clinical validation study, the authors demonstrated that VAMS is a viable alternative for imatinib monitoring in patients with chronic myeloid leukemia. For dasatinib, VAMS-based analysis may still allow for longitudinal follow-up (ie, provide insight into fluctuations in patients). As a next step, capillary microsampling can be integrated into the home sampling context.