Abstract 4362: Body mass index influences imatinib exposure in CML patients: Evidence fromTDM with adaptive dosing in real-world patients

Abstract Imatinib remains a mainstay of treatment for elderly or frail patients with chronic myeloid leukaemia (CML). Trough levels of around 1000 ng/mL are associated with a major molecular response with acceptable tolerability. We present data from 60 adult CML patients treated with imatinib on therapeutic drug monitoring (TDM) and adaptive dosing. Mean trough levels after treatment initiation were 994.2 ±560.6 ng/mL and a large inter-patient variability was observed (CV: 56%). Only 29% of patients were in the therapeutic range. All parameters associated with corpulence (i.e. body weight, height, body surface area, body mass index (BMI)) and age were significantly associated with imatinib plasma levels on univariate analysis. Age and BMI remained the only parameters associated with trough levels on multivariate analysis. As severe toxicities have been previously reported in patients with low BMI treated with standard imatinib, we evaluated the extent to which low BMI may lead to plasma overexposure. We found a statistically significant difference in trough imatinib levels in patients with BMI<18.5, with exposure +61.5% higher than in patients with 18.5<BMI<24.9 and +76.3% higher than in patients with BMI>24.9 (p<0.05, ANOVA). After TDM with adaptive dosing, a statistically significant difference in dosing between patients was observed, with doses ranging from 200 to 700 mg (p<0.001, ANOVA). No difference in toxicity or efficacy was observed regardless of BMI after adaptive dosing (p>0.05, Chi-2 test). Our data suggest that low BMI has a significant impact on imatinib exposure, but that pharmacokinetically-guided dosing limits its clinical impact in patients. Citation Format: Paul Maroselli, Raphaelle Fanciullino, Julien Colle, Laure Farnault, Pauline Roche, Geoffroy Venton, Regis Costello, Joseph Ciccolini. Body mass index influences imatinib exposure in CML patients: Evidence fromTDM with adaptive dosing in real-world patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4362.