Venetoclax联合低剂量阿糖胞苷治疗不耐受强化化疗的初治急性髓系白血病患者:一项Ⅲ期随机、安慰剂对照试验中中国队列结果  

Venetoclax with low-dose cytarabine for patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy: results from the Chinese cohort of a phase three randomized placebo-controlled trial

作　　者：胡豫[1] 金洁[2] 张钰[3] 胡建达[4] 李军民[5] 魏旭东 高素君[7] Zha Jiuhong Jiang Qi Wu Jun Wellington Mendes Andrew H.Wei 王建祥 Hu Yu;Jin Jie;Zhang Yu;Hu Jianda;Li Junmin;Wei Xudong;Gao Sujun;Zha Jiuhong;Jiang Qi;Wu Jun;Mendes Wellington;Wei Andrew H.;Wang Jianxiang(Union Hospital Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;The First Affiliated Hospital,College of Medicine,Zhejiang University,Hangzhou 310003,China;Nanfang Hospital of Southern Medical University,Guangzhou 510515,China;Fujian Medical University Union Hospital,Fuzhou 350001,China;Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;The Affiliated Cancer Hospital of Zhengzhou University,Henan Cancer Hospital,Zhengzhou 450008,China;The First Hospital of Jilin University,Changchun 130021,China;AbbVie,Inc.,Mettawa,Illinois,USA;The Alfred Hospital and Monash University,Melbourne,Victoria,Australia;Institute of Hematology and Blood Diseases Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin 300020,China)

机构地区：[1]华中科技大学同济医学院附属协和医院,武汉430022 [2]浙江大学附属第一医院,杭州310003 [3]南方医科大学南方医院,广州510515 [4]福建医科大学附属协和医院,福州350001 [5]上海交通大学医学院附属瑞金医院,200025 [6]郑州大学附属肿瘤医院、河南省肿瘤医院,450008 [7]吉林大学第一医院,长春130021 [8]AbbVie,Inc.,Mettawa,Illinois,USA [9]The Alfred Hospital and Monash University,Melbourne,Victoria,Australia [10]中国医学科学院血液病医院(中国医学科学院血液学研究所),天津300020

出　　处：《中华血液学杂志》2021年第4期288-294,共7页Chinese Journal of Hematology

摘　　要：目的:探讨Venetoclax联合低剂量阿糖胞苷(LDAC)在不能耐受强化诱导化疗的中国急性髓系白血病(AML)患者中的疗效及安全性。方法:一项Ⅲ期随机、双盲安慰剂对照试验(VIALE-C)中中国队列的结果。在本项国际临床试验中,入组了不适合接受强化化疗、新诊断为AML的18岁或以上的成人患者。在全球范围内,患者(211例)按2∶1的比例随机分配接受Venetoclax+LDAC或安慰剂+LDAC(28 d为1个周期),在第1~10天接受LDAC。主要研究终点为总生存(OS);次要研究终点包括缓解率、无事件生存期及不良事件(AE)。结果:入组15例中国患者(Venetoclax组9例;安慰剂组6例)。中位年龄为72(61~86)岁。与安慰剂组相比,Venetoclax组的死亡风险下降38%(HR=0.62,95%CI 0.12~3.07)。对延长6个月随访进行的计划外分析显示,Venetoclax组的中位OS时间为9.0个月,安慰剂组为4.1个月。完全缓解(CR)率与血细胞计数未完全恢复的CR(CRi)率分别为33%(3/9)和0(0/6)。最常见的非血液学AE(Venetoclax组与安慰剂组)为低钾血症(5/9和4/6)、呕吐(4/9和3/6)、便秘(2/9和4/6)和低白蛋白血症(1/9和4/6)。结论:Venetoclax联合LDAC在中国患者中表现出有意义的疗效和可管理的安全性特征,这与在全球VIALE-C人群中的观察结果一致,使其成为不适合接受强化化疗的新诊断AML患者的一个重要治疗选择。Objective To investigate the safety and efficacy of venetoclax with low-dose cytarabine(LDAC)in Chinese patients with acute myeloid leukemia(AML)who are unable to tolerate intensive induction chemotherapy.Methods Adults≥18 years with newly diagnosed AML who were ineligible for intensive chemotherapy were enrolled in this international,randomized,double-blind,placebo-controlled trial.Globally,patients(n=211)were randomized 2∶1 to either venetoclax with LDAC or placebo with LDAC in 28-d cycles,with LDAC on days 1-10.The primary endpoint was OS;the secondary endpoints included response rates,event-free survival,and adverse events.Results A total of 15 Chinese patients were enrolled(venetoclax arm,n=9;placebo arm,n=6).The median age was 72 years(range,61-86).For the primary analysis,the venetoclax arm provided a 38%reduction in death risk compared with the placebo[hazard ratio(HR),0.62(95%CI 0.12-3.07)].An unplanned analysis with an additional 6 months of follow-up demonstrated a median OS of 9.0 months for venetoclax compared with 4.1 months for placebo.The complete remission(CR)rates with CR with incomplete blood count recovery(CRi)were 3/9(33%)and 0/6(0%),respectively.The most common non-hematologic adverse effects(venetoclax vs placebo)were hypokalemia[5/9(56%)vs 4/6(67%)],vomiting[4/9(44%)vs 3/6(50%)],constipation[2/9(22%)vs 4/6(67%)],and hypoalbuminemia[1/9(11%)vs 4/6(67%)].Conclusion Venetoclax with LDAC demonstrated meaningful efficacy and a manageable safety profile in Chinese patients consistent with the observations from the global VIALE-C population,making it an important treatment option for patients with newly diagnosed AML who are otherwise ineligible for intensive chemotherapy.

关 键 词：白血病 髓系 急性 Venetoclax 低剂量阿糖胞苷 

分 类 号：R733.71[医药卫生—肿瘤]