Background and importance Chronic myeloid leukaemia was the first haematological neoplasia to benefit from imatinib targeted therapy. The standard dose of imatinib is 400 mg/day, although it is related to interpatient variability in plasma exposure. The relationship between treatment outcomes and plasma exposure has been established; predose plasma concentrations (Cmin) ≥1000 ng/mL are associated with improved clinical response. which supports dose optimisation through therapeutic monitoring.
Aim and objectives Our aim was to describe the degree of implementation of Cmin assessment based on response status and individual tolerance and to determine the impact of imatinib therapeutic monitoring in daily clinical practice in a tertiary hospital.
Material and methods This was an observational retrospective study in a university hospital. All patients being treated with imatinib between December 2016 and March/2019 were reviewed. Demographic and clinical data were collected (sex, diagnosis age, imatinib starting time, Cmin, BCR-ABL ratio and information concerning medical and pharmaceutical care consultation). Cmin was quantified by the nanoparticle agglutination immunoassay in human plasma.
Results Eighty-seven patients received active treatment (56% men). Age of diagnosis was 52±17 years and 74% (65/87) of patients were treated with imatinib. Treatment monitoring occurred in 66% (43/65) of patients. Time between treatment start time and Cmin monitoring was 60.8 (2.5–509) months and 2 (1–7) samples were analysed per patient: 63% (27/43) of patients had Cmin ≥1000 ng/mL since the first monitoring: 1156 (1033–2972) ng/mL (74% treated with 400 mg/day, 15% 300 mg/day, 7% 200 mg/day and 4% 600 mg/day). In 15% (4/27) of patients where appropriate Cmin was reached from the beginning, the dosage was reduced, maintaining them within optimal concentrations. In 38% (16/43) of patients, Cmin was <1000 ng/mL in the first monitored sample: 673 (444–999) ng/mL (75% treated with 400 mg/day and 25% 300 mg/day). In 88% (14/16) of patients with subtherapeutic Cmin, a new Cmin was studied: 939 (363–1352) ng/mL. In 43% (6/14) dose interventions were done (dose increased in 50% (3/6), 67% reached Cmin ≥1000ng/mL). In 57% (8/14) of patients with subtherapeutic levels, the dose was not modified due to a good treatment response (680 (525–999) ng/mL).
Conclusion and relevance Most patients reached optimal imatinib plasma concentrations with a standard dose. The results showed an outstanding implementation in clinical practice since the Cmin quantification technique was used in our hospital, mostly because of newly diagnosed patients. Recording imatinib concentrations during follow-up would help achieve 100% monitored patients. Benefits of dose optimisation include reducing the dose, keeping optimal concentrations, or increasing dose in case of subtherapeutic levels.
References and/or acknowledgements No conflict of interest.