Long-Term Follow-up of the Phase 3 Viale-a Clinical Trial of Venetoclax Plus Azacitidine for Patients with Untreated Acute Myeloid Leukemia Ineligible for Intensive Chemotherapy

威尼斯人 阿扎胞苷 医学 髓系白血病 化疗方案 内科学 化疗 白血病 肿瘤科 生物 遗传学 基因 基因表达 DNA甲基化 慢性淋巴细胞白血病
作者
Keith W. Pratz,Brian A. Jonas,Vinod Pullarkat,Michael J. Thirman,Jacqueline S. Garcia,Walter Fiedler,Kazuhito Yamamoto,Jianxiang Wang,Sung-Soo Yoon,Ofir Wolach,Jun‐Ho Jang,Su‐Peng Yeh,Grace Ku,Ying Zhou,Brenda Chyla,Jalaja Potluri,Courtney D. DiNardo
出处
期刊:Blood [Elsevier BV]
卷期号:140 (Supplement 1): 529-531 被引量:36
标识
DOI:10.1182/blood-2022-158518
摘要

Background: Venetoclax (Ven), a highly selective oral BCL-2 inhibitor, in combination with azacitidine (Aza) is approved for the treatment of patients with intensive chemotherapy-ineligible newly diagnosed AML based on the positive results of the phase 3 VIALE-A study (NCT02993523) of placebo (Pbo) vs Ven in combination with Aza in this population (DiNardo et. al. NEJM, 2020). At a median follow-up of 20.5 (range, <0.1-30.7) months (mo), with 270 death events (75% OS) in January 2020, the median overall survival (OS) was 14.7 mo for the Ven+Aza group and 9.6 mo in the Pbo+Aza group (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.52 to 0.85; P<0.001). Complete remission (CR) was higher with Ven+Aza than with Pbo+Aza (36.7% vs 17.9%; P<0.001), as was complete remission + complete remission with incomplete hematologic recovery (CR+CRi) (66.4% vs 28.3%; P<0.001) (DiNardo et. al. NEJM, 2020). While the study met the statistical significance for its primary endpoint of overall survival at the 75% OS interim analysis in March 2020, with 270 OS events, a 100% final OS analysis was undertaken with 360 survival events (data cut-off of 01 December, 2021), with 2-years of additional follow-up to determine the long-term survival benefit of Ven+Aza. Here, we present the analysis of VIALE-A, after the occurrence of 100% of the pre-planned survival events. Methods: 431 patients with confirmed AML who were previously untreated and ineligible for intensive therapy were randomly assigned 2:1 to Aza plus either Ven (286 patients) or Pbo (145 patients). All patients received a standard dose of Aza (75 mg/m2 subcutaneously or intravenously on days 1 through 7 every 28-day cycle). Ven 400 mg after a 3 day ramp up to reach the target dose in Cycle 1 or a matching Pbo was administered orally, once daily, in 28-day cycles. Results: Median age was 76 years in both groups, approximately 60% were male and 76% were Caucasian. Molecular abnormalities of interest included FLT-3, observed in 14.1% of patients receiving VEN+AZA, IDH1/2, observed in 24.9% of pts, TP53, observed in 23.3% of pts and NPM1, observed in 16.6% of pts. With a median follow-up of 43.2 mo, the median overall survival was 14.7 mo (95% CI, 12.1 to 18.7) in the Ven+Aza group and 9.6 mo (95% CI, 7.4 to 12.7) in the Pbo+Aza group (HR, 0.58; 95% CI, 0.47 to 0.72; nominal P<0.001), maintaining the survival benefit since the interim analysis in the overall population (Figure 1). At this data-cut, 49 pts remained on the study (48 in the Ven+Aza group and 1 in the Pbo+Aza group). In patients with measurable residual disease (MRD) <10-3 who had achieved CR+CRi, median OS was reached at 34.2 mo (95% CI, 27.7-44.0) in the Ven+Aza group (N=69) and 25.0 mo (95% CI, 7.0-39.8) in the Pbo+Aza group (N=11). In CR + CRi patients with MRD >10-3, median OS was 18.7 mo (95% CI, 12.9-23.5) in the Ven+Aza group (N=96) and 15.1 mo (95% CI, 7.4, 26.1) in the Pbo+Aza group (N=24). For patients in the IDH1/2 mutant subgroup, median OS was reached at final analysis, at 19.9 mo (95% CI, 12.2-27.7) in the Ven+Aza group and 6.2 mo (95% CI, 2.3-12.7) in the Pbo+Aza group (HR, 0.314; 95% CI, 0.189 to 0.522; P<0.001) (Figure 2). Overall safety profiles were comparable between Ven+Aza and Pbo+Aza. Key treatment-emergent adverse events of any grade occurring in ≥20% of pts included nausea (44.5% in the Ven+Aza group vs 36.8% in the Pbo+Aza group), diarrhea (45.2% vs 34%), and constipation (43.8% vs 39.6%). Grade 3 or higher AEs (Ven+Aza vs Pbo+Aza) occurring in ≥10% of pts included thrombocytopenia (45.9% vs 39.6%), neutropenia (42.8% vs 28.5%), and febrile neutropenia (42.8% vs 18.8%). Serious adverse events occurred in 85.1% of pts in the Ven+Aza group and 77.1% of those in the Pbo+Aza group. Further characterization of pts with long term benefit is ongoing. Conclusions: The VIALE-A long-term follow up demonstrates sustained overall survival benefit with Ven+Aza in patients with AML ineligible for intensive chemotherapy compared to Pbo+Aza in all subgroups. Notably, the median OS for patients with MRD <10-3 who had achieved CR+CRi was 34.2 mo, and median OS for patients with IDH1/2 mutations treated with Ven+Aza was 19.9 mo. The VIALE-A 2-year follow-up analysis confirms the long-term survival benefit for patients treated with Ven+Aza, with no new safety findings. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
ding应助1235采纳,获得10
1秒前
Yu发布了新的文献求助10
1秒前
活泼的惜天完成签到,获得积分10
1秒前
朝菌完成签到,获得积分10
3秒前
3秒前
李新阳完成签到,获得积分10
6秒前
6秒前
6秒前
vic关闭了vic文献求助
7秒前
ZJFL完成签到,获得积分10
7秒前
7秒前
兰蕙发布了新的文献求助10
7秒前
8秒前
8秒前
斯文败类应助笔墨留香采纳,获得50
8秒前
英姑应助Lu采纳,获得10
9秒前
11秒前
潘多拉发布了新的文献求助10
12秒前
12秒前
马夋完成签到,获得积分10
13秒前
实验顺利完成签到,获得积分10
13秒前
13秒前
大白鹅发布了新的文献求助10
14秒前
焕颜发布了新的文献求助10
14秒前
赘婿应助Leewener采纳,获得10
14秒前
zhou完成签到,获得积分10
14秒前
15秒前
15秒前
在水一方应助严冥幽采纳,获得10
17秒前
田様应助科研小白采纳,获得10
18秒前
半糖糖完成签到,获得积分10
19秒前
20秒前
雷雷发布了新的文献求助10
21秒前
笔墨留香发布了新的文献求助50
21秒前
爆米花应助天玄一刀采纳,获得10
21秒前
22秒前
华仔应助Alicyclobacillus采纳,获得10
23秒前
焕颜完成签到,获得积分20
24秒前
香蕉觅云应助畅快的涵蕾采纳,获得10
26秒前
CipherSage应助畅快的长颈鹿采纳,获得10
26秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3969917
求助须知:如何正确求助?哪些是违规求助? 3514626
关于积分的说明 11175060
捐赠科研通 3249928
什么是DOI,文献DOI怎么找? 1795165
邀请新用户注册赠送积分活动 875617
科研通“疑难数据库(出版商)”最低求助积分说明 804891