Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib
Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib
复制标题
DOI：
10.3324/haematol.2009.011452
复制
发表时间：
2010-02-01
期刊：
影响因子：
--
通讯作者：
Hochhaus, Andreas
中科院分区：
文献类型：
--
作者：
Shah, Neil P.;Kim, Dong-Wook;Hochhaus, Andreas
达沙替尼每日100毫克可间歇性抑制bcr-abl激酶，被批准用于对伊马替尼耐药或不耐药的慢性期慢性粒细胞白血病患者。为了更好地评估达沙替尼的耐受性和耐受性，本文报道了对慢性期慢性髓系白血病进行剂量优化研究的两年最低随访期的数据。设计与方法在3期研究中，670名对伊马替尼耐药、不耐受或对伊马替尼的反应不佳的慢性期慢性髓系白血病患者随机接受达沙替尼100 mg/天、50 mg/天、140 mg/天或70 mg/天的治疗。结果来自2年的最少随访数据表明，达沙替尼100 mg每天1次可获得与其他治疗组相当的主要细胞遗传学应答和完全细胞遗传学应答率并减少关键副作用的发生频率。观察到类似的两年无进展生存率和总生存率(每天服用100 mg，分别为80%和91%，其他组分别为75%-76%和88%-94%)。完全的细胞遗传学反应迅速实现，通常在6个月后。在达沙替尼每日一次治疗6个月没有完全细胞遗传学应答的患者中，对于部分细胞遗传学应答的患者来说，在2年内达到这种应答的可能性是50%，对于轻微的患者来说只有8%或更少。极小的细胞遗传学反应，或无细胞遗传学反应。不到3%的患者经历了疾病转化为加速期或急变期。结论间歇性抑制激酶可获得快速而持久的反应，与更多持续抑制的患者没有区别。
BackgroundDasatinib 100 mg once daily achieves intermittent BCR-ABL kinase inhibition and is approved for chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib. To better assess durability of response to and tolerability of dasatimb, data from a 2-year minimum follow-up for a dose-optimization study in chronic-phase chronic myeloid leukemia are reported here.Design and MethodsIn a phase 3 study, 670 chronic-phase chronic myeloid leukemia patients with resistance, intolerance, or suboptimal response to imatinib were randomized to dasatinib 100 mg once-daily, 50 mg twice-daily, 140 mg once-daily, or 70 mg twice-daily.ResultsData from a 2-year minimum follow-up demonstrate that dasatinib 100 mg once daily 0 achieves major cytogenetic response and complete cytogenetic response rates comparable to those in the other treatment arms, and reduces the frequency of key side effects. Comparable 2-year progression-free survival and overall survival rates were observed (80% and 91 %, respectively, for 100 mg once daily, and 75%-76%, and 88%-94%, respectively, in other arms). Complete cytogenetic responses were achieved rapidly, typically by 6 months. In patients treated with dasatinib 100 mg once daily for 6 months without complete cytogenetic response, the likelihood of achieving such a response by 2 years was 50% for patients who had achieved a partial cytogenetic response, and only 8%, or less for patients with minor,. minimal, or no cytogenetic response. Less than 3%, of patients suffered disease transformation to accelerated or blast phase.ConclusionsIntermittent kinase inhibition can achieve rapid and durable responses, indistinguishable from those achieved with more continuous inhibition.