Ponatinib in Japanese patients with Philadelphia chromosome-positive leukemia, a phase 1/2 study
Ponatinib in Japanese patients with Philadelphia chromosome-positive leukemia, a phase 1/2 study
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DOI：
10.1007/s12185-017-2238-9
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发表时间：
2017-09-01
影响因子：
2.1
通讯作者：
Ohyashiki, Kazuma
中科院分区：
文献类型：
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作者：
Tojo, Arinobu;Kyo, Taiichi;Ohyashiki, Kazuma
在这项正在进行的1/2期研究(NCT01667133)中，我们对Ponatinib进行了评估，并评估了对达沙替尼或尼洛替尼耐药/耐受的日本慢性髓系白血病(CML)患者，或对AE1酪氨酸激酶抑制剂(TKI)耐药/耐受的费城染色体阳性急性淋巴细胞白血病(Ph(+)ALL)患者的推荐剂量。主要终点是慢性粒细胞白血病(CP-CML)患者推荐剂量的安全性(第1期)和12个月的主要细胞遗传学反应(MCyR)，或晚期疾病(第2期)患者6个月的主要血液学反应(Mahr)。65%的CP-CML患者在12个月内达到或维持了MCyR；61%的晚期疾病患者在6个月内达到了MCyR。最常见的非血液学3/4级治疗-紧急不良事件(AE)是高血压(37%)；常见的血液学3/4级不良反应是血小板减少(57%)、中性粒细胞减少(34%)和白细胞减少(26%)。总体而言，5名患者(14%)经历了动脉闭塞事件(AOES)；没有5级AOES的报道。波纳替尼的稳态蓄积率(基于曲线下面积)介于2.6(15 mg/d)至1.3(45 mg/d)之间。总之，Ponatinib在日本CML和Ph(+)患者中证明了疗效，这些患者对以前的TKI治疗都有抵抗/耐受；安全数据支持这些患者建议的起始剂量为每天45毫克。
In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) resistant/intolerant to ae1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6 months in patients with advanced phase disease (Phase 2). MCyR was achieved/maintained by 12 months in 65% of CP-CML patients; MaHR was achieved by 6 months in 61% of patients with advanced phase disease. The most common nonhematologic grade 3/4 treatment-emergent adverse event (AE) was hypertension (37%); common hematologic grade 3/4 AEs were thrombocytopenia (57%), neutropenia (34%), and leukopenia (26%). Overall, five (14%) patients experienced arterial occlusive events (AOEs); no grade 5 AOEs were reported. The steady-state accumulation ratio of ponatinib (based on area under the curve) ranged from 2.6 (15 mg/day) to 1.3 (45 mg/day). In summary, ponatinib demonstrated efficacy in Japanese patients with CML and Ph(+)ALL resistant/intolerant to prior TKI treatment; safety data support a recommended starting dose of 45 mg/day in these patients.