Maroselli Paul, Fanciullino Raphaelle, Colle Julien, Farnault Laure, Roche Pauline, Venton Geoffroy, Costello Régis, Ciccolini Joseph
PRISM Biogénopôle La Timone University Hospital of Marseille, APHM, Marseille, France.
COMPO Centre de Recherche en Cancérologie de Marseille Inserm U1068, Marseille, France.
Fundam Clin Pharmacol. 2025 Feb;39(1):e13049. doi: 10.1111/fcp.13049.
Imatinib is the treatment of elderly or frail patients with chronic myeloid leukemia (CML). Trough levels of around 1000 ng/ml are considered as the target exposure.
We searched for baseline parameters associated with imatinib pharmacokinetics, and studied the clinical impact of subsequent adaptive dosing.
We present data from 60 adult CML patients upon imatinib with therapeutic drug monitoring (TDM) and adaptive dosing.
Mean trough levels after treatment initiation were 994.2 ± 560.6 ng/ml with 56% inter-patient variability). Only 29% of patients were in the therapeutic range. Body weight, height, body surface area, body mass index (BMI), and age were associated with imatinib plasma levels on univariate analysis. Age and BMI remained the only parameters associated with imatinib 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 kg/m, with exposure +61.5% higher than in patients with 18.5 < BMI ≤ 24.9 and +76.3% higher than in patients with BMI ≥ 25. After TDM with adaptive dosing, a statistically significant difference in dosing between patients was observed, with doses ranging from 200 to 700 mg. No difference in toxicity or efficacy was observed regardless of BMI after adaptive dosing.
Our data suggest that low BMI has a significant impact on imatinib exposure but that pharmacokinetically-guided dosing limits its clinical impact in patients.
伊马替尼用于治疗老年或体弱的慢性髓性白血病（CML）患者。约1000 ng/ml的谷浓度被视为目标暴露水平。
我们寻找与伊马替尼药代动力学相关的基线参数，并研究后续适应性给药的临床影响。
我们呈现了60例接受伊马替尼治疗并进行治疗药物监测（TDM）和适应性给药的成年CML患者的数据。
治疗开始后的平均谷浓度为994.2±560.6 ng/ml（患者间变异度为56%）。只有29%的患者处于治疗范围内。单因素分析显示，体重、身高、体表面积、体重指数（BMI）和年龄与伊马替尼血浆水平相关。多因素分析显示，年龄和BMI仍然是与伊马替尼谷浓度相关的唯一参数。由于先前有报道称，接受标准伊马替尼治疗的低BMI患者会出现严重毒性，我们评估了低BMI可能导致血浆暴露过量的程度。我们发现，BMI<18.5 kg/m²的患者伊马替尼谷浓度存在统计学显著差异，其暴露水平比BMI为18.5<BMI≤24.9的患者高61.5%，比BMI≥25的患者高76.3%。在进行TDM和适应性给药后，观察到患者之间的给药存在统计学显著差异，剂量范围为200至700 mg。适应性给药后，无论BMI如何，毒性或疗效均无差异。
我们的数据表明，低BMI对伊马替尼暴露有显著影响，但药代动力学指导的给药限制了其对患者的临床影响。
