Efficacy of molecular response at 1 or 3 months after the initiation of dasatinib treatment can predict an improved response to dasatinib in imatinib-resistant or imatinib-intolerant Japanese patients with chronic myelogenous leukemia during the chronic phase.
Efficacy of molecular response at 1 or 3 months after the initiation of dasatinib treatment can predict an improved response to dasatinib in imatinib-resistant or imatinib-intolerant Japanese patients with chronic myelogenous leukemia during the chronic phase.
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DOI：
10.3960/jslrt.54.197
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发表时间：
2014
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影响因子：
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通讯作者：
K. Inokuchi;T. Kumagai;E. Matsuki;K. Ohashi;A. Shinagawa;Y. Hatta;J. Takeuchi;C. Yoshida;H. Wakita;Y. Kozai;Y. Shirasugi;S. Fujisawa;O. Iwase;S. Yano;S. Okamoto;K. Oba;J. Sakamoto;H. Sakamaki
中科院分区：
文献类型：
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作者：
K. Inokuchi;T. Kumagai;E. Matsuki;K. Ohashi;A. Shinagawa;Y. Hatta;J. Takeuchi;C. Yoshida;H. Wakita;Y. Kozai;Y. Shirasugi;S. Fujisawa;O. Iwase;S. Yano;S. Okamoto;K. Oba;J. Sakamoto;H. Sakamaki
达沙替尼是一种 BCR-ABL 激酶抑制剂，与伊马替尼相比，其效力有所提高，其在伊马替尼耐药和伊马替尼不耐受的慢性粒细胞白血病 (CML) 患者中的有效性和安全性已得到证实。在此，一项开放标签 II 期研究评估了达沙替尼对 50 名伊马替尼耐药或伊马替尼不耐受慢性期慢性粒细胞白血病 (CML-CP) 的日本患者的疗效和安全性。达沙替尼对伊马替尼耐药和伊马替尼不耐受的患者有效。经过 12 个月的达沙替尼治疗后，35 名患者（70%）获得了主要分子缓解（MMR），16 名患者（32%）获得了完全分子缓解（CMR）。在伊马替尼耐药的 CML-CP 队列中，达沙替尼治疗 12 个月后，分别有 21 名和 8 名患者达到了 MMR 和 CMR。在伊马替尼不耐受的 CML-CP 队列中，达沙替尼治疗 12 个月后，分别有 14 名和 8 名患者达到了 MMR 和 CMR。经过 18 个月的达沙替尼治疗后，50 名患者中有 38 名 (76.0%) 达到了 MMR，19 名患者 (38.0%) 达到了 CMR。开始达沙替尼治疗后 1 或 3 个月时较低水平的 BCR-ABL 转录本与 12 和 18 个月时的 BCR-ABL 转录本水平的相关性比较高水平的 BCR-ABL 的相关性更强 (p < 0.001)。在两名接受达沙替尼治疗的患者中发现了 T315I 突变。达沙替尼总体耐受性良好，在 12 个月的随访评估中，只有 3 名患者 (5%) 由于不良血液学事件（血小板减少、贫血、中性粒细胞减少）和/或非血液学事件而停止治疗。对于伊马替尼耐药或伊马替尼不耐受的日本 CML 患者，达沙替尼是一种安全有效的治疗方法。此外，1 或 3 个月时的分子反应预测了 12 或 18 个月时对达沙替尼的反应。
Dasatinib is a BCR-ABL kinase inhibitor with improved potency compared with imatinib, for which efficacy and safety in imatinib-resistant and imatinib-intolerant patients with chronic myelogenous leukemia (CML) have been established. Here, an open-label phase II study evaluated the efficacy and safety of dasatinib in 50 Japanese patients with imatinib-resistant or imatinib-intolerant CML during the chronic phase (CML-CP). Dasatinib was effective in imatinib-resistant and imatinib-intolerant patients. After 12 months of dasatinib therapy, 35 patients (70%) had achieved a major molecular response (MMR) and 16 patients (32%) had achieved a complete molecular response (CMR). Among the imatinib-resistant CML-CP cohort, 21 and 8 patients had achieved an MMR and a CMR after 12 months of dasatinib therapy, respectively. Among the imatinib-intolerant CML-CP cohort, 14 and 8 patients had achieved an MMR and a CMR after 12 months of dasatinib therapy, respectively. After 18 months of dasatinib therapy, 38 out of 50 patients (76.0%) had achieved an MMR and 19 patients (38.0%) had achieved a CMR. A lower level of BCR-ABL transcript at 1 or 3 months after the initiation of dasatinib treatment was more strongly correlated with the BCR-ABL transcript level at 12 and 18 months (p ＜ 0.001) than a higher level of BCR-ABL. The T315I mutation was identified in two patients receiving dasatinib therapy. Dasatinib was generally well tolerated, with only 3 patients (5%) having treatment discontinuation as a result of adverse hematologic events (thrombocytopenia, anemia, neutropenia) and/or non-hematologic events at a 12-month follow-up evaluation. Dasatinib was a safe and effective treatment for Japanese patients with imatinib-resistant or imatinib-intolerant CML. In addition, the molecular response at 1 or 3 months predicted a response to dasatinib at 12 or 18 months.