Fukuda Natsuki, Akamine Yumiko, Abumiya Maiko, Takahashi Saori, Yoshioka Tomoko, Kameoka Yoshihiro, Takahashi Naoto, Miura Masatomo
Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita, Japan.
Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan.
Cancer Chemother Pharmacol. 2022 May;89(5):609-616. doi: 10.1007/s00280-022-04419-1. Epub 2022 Mar 22.
We evaluated the plasma exposure and response relationships of nilotinib for patients with newly diagnosed chronic myeloid leukemia (CML) in real-world practice.
For the 26 patients enrolled in this study, at 3, 6, 12, and 24 months after nilotinib administration, the trough plasma concentrations (C) of nilotinib were analyzed. The relationships between nilotinib C and the molecular response to nilotinib treatment at each point (each n = 26) were evaluated.
Median nilotinib C values were significantly higher in patients with a major molecular response (MMR) at 3 months than in patients without an MMR (809 and 420 ng/mL, respectively; P = 0.046). Based on the area under the receiver-operating characteristic curve, the threshold value of the nilotinib C at 3 months for predicting MMR achievement was 619 ng/mL at the best sensitivity (71.4%) and specificity (77.8%). Patients with a nilotinib C of above 619 ng/mL had a significantly shorter time to achievement of a deep molecular response (DMR; 9.0 and 18.0 months, respectively; P = 0.020) and higher rates of DMR by 2 years in Kaplan-Meier plots (P = 0.025) compared with that in patients with a nilotinib C of less than 619 ng/mL.
For patients with newly diagnosed CML, the nilotinib dose may be adjusted using a C of above 619 ng/mL as the minimum effective concentration, i.e., the lowest concentration required for MMR or DMR achievement within a shorter time, during early stages after beginning therapy to obtain faster and deeper clinical responses.
我们在真实临床实践中评估了尼罗替尼对新诊断慢性髓性白血病（CML）患者的血浆暴露量与反应关系。
本研究纳入26例患者，在给予尼罗替尼治疗后的3、6、12和24个月，分析尼罗替尼的谷血浆浓度（C）。评估各时间点（各n = 26）尼罗替尼C与尼罗替尼治疗分子反应之间的关系。
3个月时达到主要分子反应（MMR）的患者，其尼罗替尼C中位数显著高于未达到MMR的患者（分别为809和420 ng/mL；P = 0.046）。基于受试者工作特征曲线下面积，3个月时预测MMR达成的尼罗替尼C阈值为619 ng/mL，此时敏感性最佳（71.4%），特异性为（77.8%）。尼罗替尼C高于619 ng/mL的患者，达到深度分子反应（DMR）的时间显著缩短（分别为9.0和18.0个月；P = 0.020），在Kaplan-Meier曲线中，2年时DMR发生率更高（P = 0.025），而尼罗替尼C低于619 ng/mL的患者则不然。
对于新诊断的CML患者，尼罗替尼剂量可在治疗早期以高于619 ng/mL的C作为最低有效浓度进行调整，即MMR或DMR在较短时间内达成所需的最低浓度，以获得更快、更深的临床反应。
