Kimura Shinya
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Stem Cell Investig. 2016 Aug 9;3:36. doi: 10.21037/sci.2016.07.08. eCollection 2016.
ABL tyrosine kinase inhibitors (TKIs) dramatically improves chronic myeloid leukemia (CML) prognosis and most CML patients are now able to lead lives that are equivalent to those of healthy individuals. However, high cost to CML patients of long-term treatment and adverse effects (AEs) remain problems. At the setout, a clinical study involving the discontinuation of imatinib was conducted in France. Then, several stop studies of first-generation (imatinib) and second-generation ABL TKIs (dasatinib, nilotinib), which induce earlier response than imatinib, have also been started. These studies revealed that almost half of CML patients who are treated with ABL TKIs and achieve a certain period of sustained deep molecular response can stop ABL TKIs safely and obtain treatment free remission (TFR). AEs of ABL TKIs withdrawal and predicting factors for successful discontinuation including immunity are becoming clear gradually through these studies. It is important to conduct a comprehensive examination of the results of studies with a wide variety of protocols in order to determine which discontinuation method results in the highest probability of TFR in clinical settings.
ABL酪氨酸激酶抑制剂（TKIs）显著改善了慢性髓性白血病（CML）的预后，现在大多数CML患者能够过上与健康人相当的生活。然而，长期治疗对CML患者的高昂成本以及不良反应（AEs）仍然是问题。一开始，法国进行了一项关于停用伊马替尼的临床研究。随后，针对第一代（伊马替尼）和第二代ABL TKIs（达沙替尼、尼洛替尼）的多项停药研究也已启动，这些第二代药物比伊马替尼诱导反应更早。这些研究表明，接受ABL TKIs治疗并实现一定时期持续深度分子反应的CML患者中，近一半可以安全停用ABL TKIs并获得无治疗缓解（TFR）。通过这些研究，ABL TKIs停药的不良反应以及包括免疫在内的成功停药预测因素正逐渐明晰。为了确定哪种停药方法在临床环境中导致TFR的概率最高，对采用各种方案的研究结果进行全面检查很重要。
