Inokuchi Koiti, Kumagai Takashi, Matsuki Eri, Ohashi Kazuteru, Shinagawa Atsushi, Hatta Yoshihiro, Takeuchi Jin, Yoshida Chikashi, Wakita Hisashi, Kozai Yasuji, Shirasugi Yukari, Fujisawa Shin, Iwase Osamu, Yano Shingo, Okamoto Shinichiro, Oba Koji, Sakamoto Junichi, Sakamaki Hisashi
Division of Hematology, Department of Internal Medicine, Nippon Medical School.
J Clin Exp Hematop. 2014;54(3):197-204. doi: 10.3960/jslrt.54.197.
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.
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，已证实它在对伊马替尼耐药和不耐受的慢性粒细胞白血病（CML）患者中具有疗效和安全性。在此，一项开放标签的II期研究评估了达沙替尼对50例处于慢性期（CML-CP）的日本伊马替尼耐药或不耐受CML患者的疗效和安全性。达沙替尼对伊马替尼耐药和不耐受的患者有效。经过12个月的达沙替尼治疗后，35例患者（70%）达到主要分子反应（MMR），16例患者（32%）达到完全分子反应（CMR）。在伊马替尼耐药的CML-CP队列中，分别有21例和8例患者在接受12个月的达沙替尼治疗后达到MMR和CMR。在伊马替尼不耐受的CML-CP队列中，分别有14例和8例患者在接受12个月的达沙替尼治疗后达到MMR和CMR。经过18个月的达沙替尼治疗后，50例患者中有38例（76.0%）达到MMR，19例患者（38.0%）达到CMR。与较高的BCR-ABL转录水平相比，达沙替尼治疗开始后1或3个月时较低的BCR-ABL转录水平与12和18个月时的BCR-ABL转录水平相关性更强（p＜0.001）。在两名接受达沙替尼治疗的患者中检测到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例患者（5%）因血液学不良事件（血小板减少、贫血、中性粒细胞减少）和/或非血液学事件而停药。达沙替尼对日本伊马替尼耐药或不耐受的CML患者是一种安全有效的治疗方法。此外，1或3个月时的分子反应可预测12或18个月时对达沙替尼的反应。
