国产甲磺酸伊马替尼治疗儿童慢性髓系白血病慢性期的早期疗效和安全性分析

doi:10.3969/j.issn.1006-7795.2019.02.004

首都医科大学学报 ›› 2019, Vol. 40 ›› Issue (2): 174-178.doi: 10.3969/j.issn.1006-7795.2019.02.004

• 肿瘤的免疫治疗与代谢 • 上一篇下一篇

国产甲磺酸伊马替尼治疗儿童慢性髓系白血病慢性期的早期疗效和安全性分析

张利强, 陈振萍, 郑杰, 马洁, 吴润晖

国家儿童医学中心首都医科大学附属北京儿童医院血液肿瘤中心儿童血液病与肿瘤分子分型北京市重点实验室儿科学国家重点学科儿科重大疾病研究教育部重点实验室, 北京 100045

收稿日期:2019-01-17 出版日期:2019-03-21 发布日期:2019-04-15
通讯作者: 吴润晖 E-mail:runhuiwu@hotmail.com
基金资助:
国家科技重大专项（2017ZX09304029004），北京市医院管理局临床医学发展专项（ZY201404）。

A evaluation of the early efficacy and safety of generic imatinib in treating children of chronic myeloid leukemia in chronic phase

Zhang Liqiang, Chen Zhenping, Zheng Jie, Ma Jie, Wu Runhui

Beijing Key Laboratory of Pediatric Hematology Oncology;National Key Discipline of Pediatrics(Capital Medical University);Key Laboratory of Major Diseases in Children, Ministry of Education;Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China

Received:2019-01-17 Online:2019-03-21 Published:2019-04-15
Supported by:
This study was supported by National Science and Technology Key Projects (2017ZX09304029004),Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(ZY201404).

摘要/Abstract

摘要： 目的评价国产甲磺酸伊马替尼（商品名昕维）治疗新诊断儿童慢性髓系白血病慢性期（chronic phase of chronic myeloid leukemia，CP-CML）的早期血液学、细胞遗传学、分子学反应和安全性。方法收集35例从2014年1月至2018年1月在首都医科大学附属北京儿童医院初次确诊CP-CML的患儿，给予甲磺酸伊马替尼260~340 mg/m²，1次/d治疗，根据药物种类分为国产仿制药（昕维）组和进口原研药（格列卫）两组，国产仿制药（昕维）治疗组20例，原研药（格列卫）治疗组15例，随访至2018年5月。对比进口原研药，评价国产仿制药治疗CML患者3、6、12个月时的血液学、细胞遗传学和分子学反应及安全性。结果 35例初诊CP-CML患儿中位年龄10岁（1~16岁），其中男性18名，女性17名。治疗3个月时，国产仿制药组患儿完全血液学反应（complete hematologic responses，CHR）率为75%（15/20）；80%（16/20）获得主要细胞遗传学反应（minor cytogenetic response，MCyR），45%（9/20）BCR-ABL转录本水平≤ 10%。治疗6个月时，CHR率为94%（15/16）；完全细胞遗传学反应（complete cytogenetic response，CCyR）为62.5%（10/16）；43.8%（7/16）BCR-ABL ≤ 1%。治疗12个月时，CCyR为92.3%（12/13）；77%（10/13）BCR-ABL ≤ 0.1%，对比进口原研药，差异无统计学意义（P>0.05）。15%（3/20）不良反应为血液学不良反应，无严重Ⅳ级不良反应；非血液学不良反应依次为疼痛35%（7/20），消化道症状25%（5/20），水肿15%（3/20），不明原因发热10%（2/20），乏力5%（1/20），皮疹5%（1/20）。治疗3个月，国产仿制药CCyR略低于原研药（P=0.021），差异无统计学意义（P>0.05）。不良反应易控制，无药物毒性相关性死亡。结论国产甲磺酸伊马替尼初始治疗新诊断儿童CP-CML的早期血液学、细胞遗传学和分子学反应良好，安全可靠，本研究尚未发现国产仿制药与原研药在疗效和安全性上有明显差别。

关键词: 儿童, 髓系, 白血病, 伊马替尼, 仿制药

Abstract: Objective To evaluate the hematological, cytogenetic, molecular responses and safety of generic imatinib(Xinwei) in newly diagnosed patients with children of chronic phase of chronic myeloid leukemia (CP-CML). Methods Thirty-five CP-CML children patients diagnosed in Beijing Children's Hospital, Capital Medical University received oral imatinib 260-340 mg/m²,with domestic generic imatinib (Xinwei) and imported original imatinib (Gleevec), who were collected from Jan 2014 to Jan 2018 and followed up to May 2018. Compared with imported original imatinib (Gleevec) among which 20 cases were treacted with the domestic genenc imatinib (Xinwei) and 15 cases were treated with the imported original imatinib (Gleevec), hematological responses, cytogenetic examinations, BCR-ABL transcript levels, and the safety with domestic generic imatinib treatment were monitored after 3,6, and 12 month treatment. Results A total of 35 children CP-CML patients (18 males and 17 females with a median age of 10 years) were collected among which 20 cases were treated with the domestic generic imatinib (Xinwei), and 15 cases were treated with the imported original imatinib (Gleevec). At 3-month, the domestic generic imatinib group 75% (15/20) patients achieved the complete hematologic responses (CHR), and patients with minor cytogenetic response (MCyR) or BCR-ABL ≤ 10% were 80%(16/20) and 45%(9/20), respectively. At 6-month, 94%(15/16) patients achieved CHR, patients with complete cytogenetic response(CCyR) and BCR-ABL ≤ 1% was 62.5%(10/16) and 43.8%(7/16). At 12-month, 92.3%(12/13) CCyR and 77%(10/13)BCR-ABL ≤ 0.1%. There was no significant difference between two group at all stages (P>0.05). The hematologic toxicity occurred in 15%(3/20),with no grade Ⅲ hematologic toxicity. The non-hematologic toxicities included pain 35%(7/20),gastrointestinal reaction 25%(5/20), edema 15%(3/20), fever 10%(2/20),fatigue 5%(1/20), and rash 5%(1/20). Compared with imported original imatinib, CCyR was lower in generic imatinib group at 3-month (P=0.021). There was no other significant difference (P>0.05). The adverse reactions were easy to control and there were no drug-related deaths.Conclusion Generic imatinib has a good efficacy in the hematological, cytogenetic molecular reponses with CP-CMP patients in newly diagnosed, without serious adverse reactions. There is no significant difference in efficacy and safety between generic and imported original imatinib in our study.

Key words: children, myeloid, leukemia, imatinib, generic drug

中图分类号:

R733

张利强, 陈振萍, 郑杰, 马洁, 吴润晖. 国产甲磺酸伊马替尼治疗儿童慢性髓系白血病慢性期的早期疗效和安全性分析[J]. 首都医科大学学报, 2019, 40(2): 174-178.

Zhang Liqiang, Chen Zhenping, Zheng Jie, Ma Jie, Wu Runhui. A evaluation of the early efficacy and safety of generic imatinib in treating children of chronic myeloid leukemia in chronic phase[J]. Journal of Capital Medical University, 2019, 40(2): 174-178.

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国产甲磺酸伊马替尼治疗儿童慢性髓系白血病慢性期的早期疗效和安全性分析

A evaluation of the early efficacy and safety of generic imatinib in treating children of chronic myeloid leukemia in chronic phase

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