国产甲磺酸伊马替尼治疗初诊慢性髓系白血病慢性期的临床研究

马军; 罗建民; 闻艳; 曹志坚; 李书芹; 马晓军; 张曦; 曾云; 陈协群; 焦宗久; 郝洪岭; 苏毅; 吴德沛; 杨建民; 谭获; 吴诗馨

doi:10.13201/j.issn.1004-2806.2018.11.007

国产甲磺酸伊马替尼治疗初诊慢性髓系白血病慢性期的临床研究

- 1. 哈尔滨血液病肿瘤研究所(哈尔滨, 150010);
- 2. 河北医科大学第二医院;
- 3. 云南省第一人民医院;
- 4. 邯郸市中心医院;
- 5. 第三军医大学附属新桥医院;
- 6. 昆明医科大学第一附属医院;
- 7. 空军军医大学西京医院;
- 8. 邢台市人民医院;
- 9. 河北省人民医院;
- 10. 成都军区总医院;
- 11. 苏州大学附属第一医院;
- 12. 上海长海医院;
- 13. 广州医学院附属第一医院;
- 14. 福建医科大学附属第二医院

详细信息

通讯作者: 马军,E-mail:majun0322@126.com

中图分类号: R733.72

收稿日期: 2018-07-20

Clinical study of domestic imatinib mesylate in the treatment of newly diagnosed chronic myeloid in chronic phase

- 1. Harbin Institute of Hematology and Oncology, Harbin, 150010, China;
- 2. The Second Hospital of Hebei Medical University;
- 3. The First People's Hospital of Yunnan Province;
- 4. HanDan Central Hospital;
- 5. Xinqiao Hospital Affiliated to the Third Military Medical University;
- 6. First Affiliated Hospital of Kunming Medical University;
- 7. Xijing Hospital, Air Force Military Medical University;
- 8. Xingtai People's Hospital;
- 9. Hebei General Hospital;
- 10. Chengdu Military General Hospital;
- 11. The First Affiliated Hospital of Soochow University;
- 12. Changhai Hospital of Shanghai;
- 13. The First Affiliated Hospital of Guangzhou Medical College;
- 14. The Second Affiliated Hospital of Fujian Medical University

More Information

Corresponding author: MA Jun, E-mail: majun0322@126.com

Received Date: 20 July 2018

摘要

摘要: 目的:评价国产甲磺酸伊马替尼治疗初诊慢性髓系白血病慢性期(CML-CP)的疗效和安全性。方法:94例初诊的CML-CP患者接受口服国产甲磺酸伊马替尼治疗,400 mg/次,每日1次,评价治疗3、6、12个月时的血液学、细胞遗传学和分子学反应以及安全性。结果:94例CML-CP患者均治疗 ≥ 3个月,其中治疗 ≥ 6个月者87例,治疗 ≥ 12个月者78例。治疗满3个月时,88例(93.6%)获得完全血液学反应(CHR)。51例患者进行了细胞遗传学检查,18例(35.3%)获得主要细胞遗传学反应(MCyR),其中7例(13.7%)获得完全细胞遗传学反应(CCyR)。94例患者均进行BCR-ABL融合基因转录本水平检测,其中BCR-ABL ≤ 10%的患者有68例(72.3%),达到主要分子学反应(MMR:BCR-ABL ≤ 0.1%)的患者有9例(9.6%)。治疗满6个月时,85例(97.7%)获得CHR。48例患者进行了细胞遗传学检查,34例(70.8%)获得MCyR,其中17例(35.4%)获得CCyR。87例患者均进行BCR-ABL融合基因转录本水平检测,BCR-ABL ≤ 1%的患者有44例(50.6%),达到MMR的患者15例(17.2%)。治疗满12个月时,所有患者(100%)获得CHR。60例患者进行了细胞遗传学检查,49例(81.7%)获得MCyR,其中41例(68.3%)获得CCyR。78例患者进行BCR-ABL融合基因转录本水平检测,达到MMR的患者22例(28.2%)。Ⅲ级白细胞减少、血小板减少以及贫血的发生率分别为8.5%、2.1%、4.3%,无Ⅳ级血液学不良反应发生。非血液学不良反应依次为恶心(51.1%)、呕吐(30.9%)、疲劳(7.4%)、皮疹(23.4%)、发热(12.8%)、头痛(14.9%)、腹泻腹痛(37.2%)、周围浮肿(51.1%)、肝功能异常(6.4%),多为Ⅰ~Ⅱ级,Ⅲ级非血液学不良反应极少见,仅5例(5.3%)患者发生Ⅲ级皮疹,无一例患者出现Ⅳ级非血液学不良反应。结论:国产甲磺酸伊马替尼治疗初诊CML-CP的早期疗效肯定,安全性良好。
- 慢性髓系白血病慢性期 /
- 伊马替尼 /
- 国产 /
- 疗效 /
- 安全性
Abstract: Objective:To evaluate the early clinical efficacy and safety in newly diagnosed patients with chronic myelogenous leukemia in chronic phase (CML-CP) and initially treated with domestic imatinib mesylate.Method:A total of 94 newly diagnosed patients of CML-CP were treated with domestic imatinib mesylate 400 mg/qd po.The hematologic,cytogenetic and molecular responses were assessed at 3,6 and 12 month and adverse events were evaluated.Result:The 94 patients were treated with domestic imatinib mesylate ≥ 3 months,87 of them were treated ≥ 6 months and 78 of them were treated ≥ 12 months.At the 3rd month,the complete hematologic responses (CHR) rate was 93.6%,meanwhile 18/51(35.3%) patients had major cytogenetic response (MCyR) and 7/51(13.7%) patients had complete cytogenetic response (CCyR);BCR-ABL^IS was ≤ 10% in 68/94 patients (72.3%),moreover,9 of them (9.6%) had major molecular response (MMR:BCR-ABL^IS was ≤ 0.1%).At the 6th month,the CHR rate was 97.7%(85/87);34/48 patients (70.8%) had MCyR;17/48 patients (35.4%) had CCyR;BCR-ABL^IS was ≤ 1% in 44/87 patients (50.6%),and 15 of them (17.2%) had MMR.At the 12th month,the CHR rate was 100%(94/94);49/60 patients (81.7%) had MCyR;41/60 patients (68.3%) had CCyR;22/78 patients (28.2%) had MMR.The adverse event rate in grade Ⅲ with leucopenia,thrombocytopenia and anemia was 8.5%,2.1% and 4.3%,respectively.There was no hematology adverse events in grade Ⅳ.The non-hematologic adverse events were nausea (51.1%),emesis (30.9%),fatigue (7.4%),rash (23.4%),fever (12.8%),headache (14.9%),abdominal pain of diarrhoea (37.2%),peripheral edema (51.1%),and impaired liver function (6.4%),mostly gradeⅠ-Ⅱ.Grade Ⅲ non-hematological adverse events were rare,only 5 cases (5.3%) had grade Ⅲ rash.No patient experienced grade Ⅳ non-hematologic adverse events.Conclusion:The study reveals the excellent early clinical efficacy and safety in CML-CP treated with domestic imatinib mesylate in the early stage.
- chronic myeloid leukemia in chronic phase /
- imatinib /
- domestic /
- clinical efficacy /
- safety

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参考文献(24)

[1]	Quintás-Cardama A,Cortes J.Molecular biology of bcr-abl1-positive chronicmyeloid leukemia[J].Blood,2009,113:1619-1630.
[2]	Rowley JD.Letter:a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining[J].Nature,1973,243:290-293.
[3]	Deininger MW,Goldman JM,Melo JV.The molecular biology of chronic myeloid leukemia[J].Blood,2000,96:3343-3356.
[4]	O'Brien SG,Guilhot F,Goldman JM,et al.International randomized study of interferon versus STI571(IRIS)7-year follow-up:sustained survival,low rate of transformation and increased rate of major molecular response (MMR) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib (IM)[J].Blood,2008,112:Abstract 186.
[5]	Cortes JE,Talpaz M,O'Brien S,et al.Staging of chronic myeloid leukemiain the imatinib era:an evaluation of the World Health Organization proposal[J].Cancer,2006,106:1306-1315.
[6]	Bonzheim I,Mankel B,Klapthor P,et al.CALR-mutated essential thrombocythemia evolving to chronic myeloid leukemia with coexistent CALR mutation and BCR-ABL translocation[J].Blood,2015,125:2309-2311.
[7]	Thielen N,van der Holt B,Cornelissen JJ,et al.Imatinib discontinuation in chronic phase myeloid leukaemia patients in sustained complete molecular response:a randomised trial of the Dutch-Belgian Cooperative Trial for Haemato-Oncology (HOVON)[J].Eur J Cancer,2013,49:3242-3246.
[8]	Druker BJ,Talpaz M,Resta DJ,et al.Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia[J].N Engl J Med,2001,344:1031-1037.
[9]	Kantarjian H,Sawyers C,Hochhaus A,et al.Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia[J].N Engl J Med,2002,346:645-652.
[10]	O'Brien SG,Guilhot F,Larson RA,et al.Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia[J].N Engl J Med,2003,348:994-1004.
[11]	Druker BJ,Guilhot F,O'Brien SG,et al.Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia[J].N Engl J Med,2006,355:2406-2417.
[12]	Hochhaus A,O'Brien SG,Guilhot F,et al.Six-year follow-up of patients receiving imatinib for the fist-line treatment of chronic myeloid leukemia[J].Leukemia,2009,23:1054-1061.
[13]	Hochhaus A,Larson RA,Guilhot F,et al.Long-term outcomes of imatinib treatment for chronic myeloid leukemia[J].N Engl J Med,2017,376:917-927.
[14]	Kalmanti L,Saussele S,Lauseker M,et al.Safety and efficacy of imatinib in CML over a period of 10 years:data from the randomized CML.Study Ⅳ[J].Leukemia,2015,29:1123-1132.
[15]	NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines):Chronic Myelogenous Leukemia[S/OL].Version1,2016.http://www.nccn.org/professionals/physician-gls/f-guidelines.asp.
[16]	中华医学会血液学分会实验诊断学组,中国慢性髓性白血病联盟专家组.中国慢性髓性白血病诊疗监测规范[J].中华血液学杂志,2014,35(8):1-4.
[17]	San Juan AA.Structural investigation of PAP derivatives by CoMFA and CoMSIA reveals novel insight towards inhibition of Bcr-Abl oncoprotein[J].J Mol Graph Model,2007,26:482-493.
[18]	Hugues L,Jane FA,Jamshid SK,et al.Imatinib for newly diagnosed patients with chronic myeloid leukemia:incidence of sustained responses in an intention-to-treat analysis[J].J Clin Oncol,2008,26:3358-3363.
[19]	Jorge EC,Michele B,Fran G,et al.Phase III,randomized,open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed,previously untreated chronic myeloid leukemia in chronic phase using molecular end points:Tyrosine Kinase Inhibitor Optimization and Selectivity Study[J].J Clin Oncol,2010,28:424-430.
[20]	Hagop K,Neil PS,Andreas H,et al.Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia[J].N Engl J Med,2010,362:2260-2270.
[21]	Kim DD,Hamad N,Lee HG,et al.BCR/ABL level at 6 months identifies good risk CML subgroup after failing early molecular response at 3 months following imatinib therapy for CML in chronic phase[J].Am J Hematol,2014,89:626-632.
[22]	Hochhaus A,Saglio G,Hughes TP,et al.Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase:5-year update of the randomized ENESTnd trial[J].Leukemia,2016,30:1044-1054.
[23]	Hanfstein B,Shlyakhto V,Lauseker M,et al.Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib[J].Leukemia,2014,28:1988-1992.
[24]	Branford S,Yeung DT,Parker WT,et al.Prognosis for patients with CML and>10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline[J].Blood,2014,124:511-518.