Therapeutic drug monitoring of imatinib in paediatric chronic myeloid leukaemia: Data from a real-world setting.

Imatinib (IMA) therapy for paediatric chronic myeloid leukemia (pCML) requires age-dependent dose adjustments. Assessment of therapeutic drug monitoring (TDM) under 'real-world' conditions was performed. Collection of blood and TDM-relevant data, calculation of individual dosage exposure, measurement of plasma Cmin (IMA, Nor-IMA) by HPLC/MS-MS and recording of adverse event (AE). Two hundred and forty-six specimens from 66 patients were analysed. Individual median IMA dosage exposure was 253 mg/m2 (range: 128-504). Children <13 years received a median of 43 mg/m2 more than older patients (p < 0.0001). Median Cmin of IMA and Nor-IMA was 1017 ng/mL (range: 51-3976) and 269 ng/mL (range: 21-981), respectively, correlating significantly with the prescribed dose. At 5/246 visits, non-adherence was confirmed by very low IMA Cmin in 3/66 patients, all ≥13 years old. Correlation of IMA Cmin >1000 ng/mL with achieving OMR demonstrated in each 63% (N = 24/37, N = 27/43, respectively) patients at months 3 and 6. In the cohort with lower levels, only 23% and 50%, respectively, achieved these milestones. This difference was significant only at month 3. Of 66 patients, 30 reported 125 AEs with gastrointestinal and musculoskeletal as leading complaints. In 9.3% of AEs, the correlated IMA Cmin was ≥3000 ng/mL. TDM is a simple and rapid additional tool for managing pCML under 'real-world conditions'.