Imatinib plasma trough levels in chronic myeloid leukaemia: results of a multicentre study CSTI571AIL11TGLIVEC
Imatinib plasma trough levels in chronic myeloid leukaemia: results of a multicentre study CSTI571AIL11TGLIVEC
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DOI：
10.1002/hon.2005
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发表时间：
2012-12-01
影响因子：
3.3
通讯作者：
Nagler, Arnon
中科院分区：
文献类型：
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作者：
Koren-Michowitz, Maya;Volchek, Yulia;Nagler, Arnon
伊马替尼已被接受为慢性粒细胞白血病（CML）患者的一线治疗，患者通常接受的剂量范围为400至800？mg/天。以往的研究表明，维持伊马替尼血药浓度（IMPLs）>1000？ng/mL可改善缓解和长期结局。然而，IMPL在患者中因药物相互作用、粘附、毒性和细胞外排/内流蛋白表达水平差异等因素而异。本研究分析了191例CML患者的IMPL，并与分子和细胞遗传学缓解（CyR）进行了比较。IMPL还与肾功能和肝功能障碍相关。此外，还监测了自我报告的依从性。IMPL的中位数和平均值为994？ng/mL和1070+/-686？ng/mL，分别与96例（50%）达到血浆水平>1000？ng/mL。患者自我报告的依从性为98%。达到完全CyR（CCyR）的患者的IMPL显著较高（1078 ± 545？ng/mL）高于无CyR的（827+/-323？ng/mL，p？=？0.045）。当分组在一起时，实现CCyR或部分CyR的患者的IMPL显著高于实现最小CyR或未实现CyR的患者（1066？ng/mL vs 814？ng/mL，p？=？0.002）。在获得分子学缓解的患者之间，IMPL无显著差异（n = 10）。177)治疗（主要分子反应，976+/-385？ng/mL与完全分子学缓解，1138+/-809？ng/mL，p？=？0.387）。有或无肾或肝损害的患者的平均IMPL相似。总体而言，该研究证实了先前的报告，即较高的IMPL与临床应答相关，并证明伊马替尼暴露在有或无肝和/或肾功能不全的患者中没有差异。IMPL检测和患者日记的使用可能是CML患者伊马替尼治疗管理的实用工具。版权所有（c）2012约翰威利父子有限公司
Imatinib has been accepted as frontline treatment for patients with chronic myeloid leukaemia (CML), and patients generally receive doses ranging from 400 to 800?mg/day. Previous studies have demonstrated that maintaining imatinib plasma levels (IMPLs) >1000?ng/mL leads to improved responses and long-term outcomes. However, IMPLs vary among patients because of factors such as drugdrug interactions, adherence, toxicity and differential levels of expression of cellular efflux/influx proteins. In this study, IMPLs were analysed in 191 patients with CML and were compared with achievement of molecular and cytogenetic responses (CyR). IMPLs were also correlated with renal and hepatic dysfunction. Additionally, self-reported adherence was monitored. The median and mean IMPLs were 994?ng/mL and 1070+/-686?ng/mL, respectively, with 96 patients (50%) achieving plasma levels >1000?ng/mL. Self-reported patient compliance was 98%. Patients who achieved a complete CyR (CCyR) had significantly higher IMPLs (1078+/-545?ng/mL) than those without CyR (827+/-323?ng/mL, p?=?0.045). When grouped together, patients who achieved a CCyR or partial CyR had significantly higher IMPLs than patients who achieved a minimal CyR or did not achieve a CyR (1066?ng/mL vs 814?ng/mL, p?=?0.002). There was no significant difference observed in the IMPLs between patients who achieved molecular responses (n?=?177) on treatment (major molecular response, 976+/-385?ng/mL versus complete molecular response, 1138+/-809?ng/mL, p?=?0.387). Mean IMPLs were similar in patients with or without renal or hepatic impairment. Overall, this study confirmed previous reports that higher IMPLs correlate with clinical responses and demonstrated that imatinib exposure did not differ in patients with or without liver and/or renal dysfunction. The use of IMPL testing and patient diaries may be practical tools for the management of imatinib therapy in patients with CML. Copyright (c) 2012 John Wiley & Sons, Ltd.