Kim Dong-Wook
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Korean J Hematol. 2011 Sep;46(3):169-74. doi: 10.5045/kjh.2011.46.3.169. Epub 2011 Sep 30.
Through the phase 3 International Randomized Study of Interferon vs. STI571 (IRIS) trial, imatinib emerged as the standard treatment for chronic myeloid leukemia (CML) and has successfully prolonged the duration of both the chronic phase (CP) and the disease-free state. The majority of newly diagnosed patients treated for CP-CML achieve a complete cytogenetic response (CCyR), and over time, most of these eventually achieve major molecular responses (MMRs) and even complete molecular responses (CMRs). In ongoing phase 3 randomized trials of second-generation tyrosine kinase inhibitors (TKIs), nilotinib and dasatinib have been found to have superior efficacies in helping achieve cytogenetic and molecular responses, including MMRs and CMRs. However, only the MMR rate was significantly higher in bosutinib compared with the imatinib control, but not in CCyR rate. Current reports of imatinib discontinuation suggested that achieving CMR is an important prerequisite for CML to be cured. Recent data from the STIM (Stop Imatinib) trial showed that imatinib can be successfully discontinued in patients who achieve a certain level of CMR. Standardized real-time quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR) assays have been available in routine clinical practice, and efforts are being focused on achieving higher sensitivity and optimizing the time of imatinib discontinuation. Although very few patients are cured by administration of only Bcr-Abl TKIs, including imatinib and second-generation TKIs, current advances may eventually make this possible. This report summarizes the detailed clinical data obtained in the DASISION, ENESTnd, and BELA studies and discusses high-sensitivity detection methods and future therapeutic strategies.
通过3期干扰素与STI571国际随机研究（IRIS）试验，伊马替尼成为慢性髓性白血病（CML）的标准治疗方法，并成功延长了慢性期（CP）和无病状态的持续时间。大多数接受CP-CML治疗的新诊断患者实现了完全细胞遗传学缓解（CCyR），随着时间的推移，其中大多数最终实现了主要分子反应（MMR）甚至完全分子反应（CMR）。在正在进行的第二代酪氨酸激酶抑制剂（TKI）3期随机试验中，已发现尼罗替尼和达沙替尼在帮助实现细胞遗传学和分子反应（包括MMR和CMR）方面具有更高的疗效。然而，与伊马替尼对照组相比，博舒替尼仅MMR率显著更高，而CCyR率则不然。目前关于停用伊马替尼的报告表明，实现CMR是治愈CML的重要前提。STIM（停止伊马替尼）试验的最新数据表明，在达到一定水平CMR的患者中可以成功停用伊马替尼。标准化的实时定量逆转录聚合酶链反应（RQ-PCR）检测已应用于常规临床实践，目前的工作重点是提高敏感性并优化伊马替尼停药时间。虽然仅使用Bcr-Abl TKI（包括伊马替尼和第二代TKI）治愈的患者很少，但目前的进展最终可能使其成为可能。本报告总结了在DASISION、ENESTnd和BELA研究中获得的详细临床数据，并讨论了高灵敏度检测方法和未来的治疗策略。
