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首次缓解期急性髓系白血病应用口服阿扎胞苷维持治疗
Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission


Andrew H. Wei ... 肿瘤 • 2020.12.24
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• 急性髓系白血病患者缓解期的维持治疗 • 阿扎胞苷联合维奈托克治疗未经治疗的急性髓系白血病 • gilteritinib与化疗治疗复发性或难治性FLT3突变型AML的比较 • 米哚妥林联合化疗治疗FLT3基因突变急性髓系白血病的研究

阿扎胞苷口服剂可显著延长复发老年AML患者生存期

 

贡铁军,马军*

哈尔滨血液病肿瘤研究所

*通讯作者

 

急性髓系白血病(AML)是以骨髓与外周血中原始和幼稚髓细胞异常增生为主要特征的一类白血病。大多数患者病情急重,预后差。克隆进化、表观遗传重编程导致的异常DNA甲基化使白血病起始细胞长期存在。

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摘要


背景

虽然诱导化疗可使许多老年急性髓系白血病(AML)患者达到缓解,但复发的情况常见,且总生存期较短。

 

方法

我们开展了一项3期、随机、双盲、安慰剂对照试验,本试验将阿扎胞苷口服制剂(CC-486,一种与阿扎胞苷注射剂不具有生物等效性的低甲基化药物)作为强化化疗后首次缓解期的AML患者的维持治疗。我们将年龄≥55岁、处于完全缓解期(全血细胞计数恢复或未恢复)且不适合接受造血干细胞移植的患者随机分组,两组分别接受每日1次CC-486(300 mg)或安慰剂治疗,每28日一个周期,每个周期用药14日。主要终点是总生存期。次要终点包括无复发生存期和健康相关生活质量。

 

结果

共计472例患者被随机分组,其中238例被分配至CC-486组,234例被分配至安慰剂组。中位年龄为68岁(范围,55~86)。在CC-486组中,从随机分组开始计算的中位总生存期显著超过安慰剂组(分别为24.7个月和14.8个月;P<0.001)。CC-486组的中位无复发生存期也显著超过安慰剂组(分别为10.2个月和4.8个月;P<0.001)。CC-486在总生存期和无复发生存期方面有益处见于根据基线特征定义的大多数亚组。两组最常见的不良事件均为1级或2级胃肠道事件。常见的3级或4级不良事件包括中性粒细胞减少(CC-486组41%的患者和安慰剂组24%的患者)和血小板减少(分别为22%和21%)。患者在CC-486治疗期间可保持总体健康相关生活质量。

 

结论

在化疗后缓解期的老年AML患者中,与安慰剂相比,CC-486维持治疗与显著较长的总生存期和无复发生存期相关。副作用主要包括胃肠道症状和中性粒细胞减少。患者在整个治疗期间可维持生活质量指标(由赛尔基因[Celgene]资助,QUAZAR AML-001在ClinicalTrials.gov注册号为NCT01757535)。





作者信息

Andrew H. Wei, M.B., B.S., Ph.D., Hartmut Döhner, M.D., Christopher Pocock, M.B., B.S., Pau Montesinos, M.D., Ph.D., Boris Afanasyev, M.D., D.Sci., Hervé Dombret, M.D., Farhad Ravandi, M.D., Hamid Sayar, M.D., Jun-Ho Jang, M.D., Ph.D., Kimmo Porkka, M.D., Dominik Selleslag, M.D., Irwindeep Sandhu, M.D., Mehmet Turgut, M.D., Valentina Giai, M.D., Ph.D., Yishai Ofran, M.D., Merih Kizil Çakar, M.D., Aida Botelho de Sousa, M.D., Justyna Rybka, M.D., Ph.D., Chiara Frairia, M.D., Lorenza Borin, M.D., Germana Beltrami, M.D., Jaroslav Čermák, M.D., Ph.D., Gert J. Ossenkoppele, M.D., Ph.D., Ignazia La Torre, M.D., Barry Skikne, M.D., Keshava Kumar, Ph.D., Qian Dong, Dr.P.H., C.L. Beach, Pharm.D., and Gail J. Roboz, M.D. for the QUAZAR AML-001 Trial Investigators†
From the Department of Clinical Haematology, Alfred Hospital, and the Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia (A.H.W.); the Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany (H. Döhner); Kent and Canterbury Hospital, Canterbury, United Kingdom (C.P.); Centro de Investigación Biomédica en Red de Cáncer, Instituto Carlos III, Madrid, and Hospital Universitari i Politècnic La Fe, Valencia — both in Spain (P.M.); Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology, and Transplantation, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia (B.A.); the Department of Hematology, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris, and Institut de Recherche Saint-Louis, Université de Paris, Paris (H. Dombret); the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston (F.R.); Indiana University Cancer Center, Indianapolis (H.S.); Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (J.H.J.); Hospital District of Helsinki and Uusimaa (HUS) Comprehensive Cancer Center, Hematology Research Unit Helsinki and iCAN Digital Precision Cancer Center Medicine Flagship, University of Helsinki, Helsinki (K.P.); AZ Sint-Jan Brugge-Oostende AV, Bruges, Belgium (D.S.); University of Alberta Hospital, Edmonton, Canada (I.S.); Ondokuz Mayis University, Samsun (M.T.), and Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara (M.K.C.) — both in Turkey; Antonio e Biagio e Cesare Arrigo Hospital, Alessandria (V.G.), Città della Salute e della Scienza, Turin (C.F.), Ospedale San Gerardo Monza, Monza (L.B.), and Ospedale Policlinico San Martino, Genoa (G.B.) — all in Italy; Rambam Medical Center and Faculty of Medicine Technion, Haifa, Israel (Y.O.); Hospital dos Capuchos, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal (A.B.S.); Wroclaw Medical University, Wroclaw, Poland (J.R.); Ústav Hematologie a Krevní Transfuze, Prague, Czech Republic (J.C.); Amsterdam University Medical Center, Location VUMC (Vrije Universiteit Medical Center), Amsterdam (G.J.O.); Celgene (Bristol Myers Squibb), Boudry, Switzerland (I.L.T.); Bristol Myers Squibb, Princeton, NJ (B.S., K.K., Q.D., C.L.B.); University of Kansas Medical Center, Kansas City (B.S.); and Weill Cornell Medicine and New York Presbyterian Hospital, New York (G.J.R.). Address reprint requests to Dr. Wei at Alfred Hospital, Commercial Rd., Melbourne, VIC 3004, Australia, or at andrew.wei@monash.edu. Boris Afanasyev, M.D., D.Sci., is deceased. † A list of the principal investigators in the QUAZAR AML-001 trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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