维奈托克与去甲基化药物对比诱导化疗用于新诊断急性髓系白血病患者：一项系统评价和荟萃分析

Venetoclax and hypomethylating agents versus induction chemotherapy for newly diagnosed acute myeloid leukemia patients: a systematic review and meta-analysis.

作者信息

Liu Yun, Zhang Ying, Gao Jinhong, Wang Lijuan, Xie Fang, Zhang Chengtao, Mao Peimin, Yan Jinsong

机构信息

Department of Hematology, The Second Hospital of Dalian Medical University, Dalian, China.

Department of Hematology, Weifang People's Hospital, Shandong Second Medical University, Weifang, Shandong, China.

出版信息

BMC Cancer. 2025 May 19;25(1):894. doi: 10.1186/s12885-025-14311-9.

DOI:10.1186/s12885-025-14311-9

PMID:40389911

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12090470/

Abstract

BACKGROUND

Venetoclax with hypomethylating agents (VEN-HMAs) has shown inconsistent efficacy versus induction chemotherapy (IC) in newly diagnosed AML (ND-AML). Whether or not VEN-HMAs are of clinical benefit remains uncertain. We conducted this meta-analysis to evaluate the clinical benefit of VEN-HMAs versus IC in various subtypes of ND-AML.

METHODS

We searched PubMed, Embase, Cochrane Library, and Web of Science databases up to 17 June 2024. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Data were extracted to perform meta-analysis or descriptive analysis. The random-effects model was used to calculate the effect sizes and 95% confidence interval (CI). Relative risk (RR) was used to estimate complete response (CR), CR/ complete response with incomplete blood count recovery (CRi), overall response rate (ORR), and 30-day mortality. Hazard ratio (HR) was used to evaluate overall survival (OS) data.

RESULTS

Fifteen retrospective cohort studies with 3809 participants were identified. Compared to the IC group, the pooled RR estimates for VEN-HMAs were 1.05 (95% CI 0.88-1.26, P = 0.591) for CR, 1.09 (95% CI 0.96-1.23, P = 0.195) for CR/ CRi, 0.84 (95% CI 0.60-1.18, P = 0.318) for ORR, and 0.86 (95% CI 0.50-1.49; P = 0.596) for 30-day mortality. VEN-HMAs prolonged the OS advantage in the ND-AML population (HR = 0.80, 95% CI 0.66-0.97, P = 0.025), and was demonstrated in patients with nucleophosmin 1 (NPM1) mutation (HR = 0.64, 95% CI 0.44-0.92, P = 0.017). In AML patients with RUNX1::RUNX1T1 cytogenetic abnormalities, the pooled ORR was lower in the VEN-HMAs group (RR = 0.44, 95% CI 0.28-0.69, P < 0.001), but OS was of no significantly different (HR = 1.30, 95% CI 0.52-3.26,P = 0.58). However, only 2 studies were available and the results should be taken with caution. OS benefit was similar in other subgroup analyses based on cytogenetic risk, age, and AML type (de novo, secondary, treatment-related or prior therapy for myeloid disease cohort).

CONCLUSION

Compared with the IC group, VEN-HMAs improved OS in ND-AML, especially in the NPM1 mutation subgroup (HR = 0.64), ensured the efficacy of CR, CR/CRi and ORR, without increasing 30-day mortality, necessitating further head-to-head randomized controlled trials (RCTs).

TRIAL REGISTRATION

This trial was registered with PROSPERO ( www.crd.york.ac.uk/prospero/ ) on 13 July 2024, the registration number is CRD42024560585.

摘要

背景

维奈克拉联合低甲基化药物（VEN-HMAs）在新诊断的急性髓系白血病（ND-AML）中与诱导化疗（IC）相比，疗效并不一致。VEN-HMAs是否具有临床益处仍不确定。我们进行了这项荟萃分析，以评估VEN-HMAs与IC在ND-AML各亚型中的临床益处。

方法

我们检索了截至2024年6月17日的PubMed、Embase、Cochrane图书馆和Web of Science数据库。使用纽卡斯尔-渥太华量表（NOS）评估纳入研究的质量。提取数据以进行荟萃分析或描述性分析。采用随机效应模型计算效应量和95%置信区间（CI）。相对风险（RR）用于估计完全缓解（CR）、伴有血细胞计数未完全恢复的完全缓解（CRi）、总缓解率（ORR）和30天死亡率。风险比（HR）用于评估总生存期（OS）数据。

结果

确定了15项回顾性队列研究，共3809名参与者。与IC组相比，VEN-HMAs组CR的合并RR估计值为1.05（95%CI 0.88-1.26，P = 0.591），CR/CRi为1.09（95%CI 0.96-1.23，P = 0.195），ORR为0.84（95%CI 0.60-1.18，P = 0.318），30天死亡率为0.86（95%CI 0.50-1.49；P = 0.596）。VEN-HMAs延长了ND-AML人群的OS优势（HR = 0.80，95%CI 0.66-0.97，P = 0.025），在核磷蛋白1（NPM1）突变患者中也得到证实（HR = 0.64，95%CI 0.44-0.92，P = 0.017）。在伴有RUNX1::RUNX1T1细胞遗传学异常的AML患者中，VEN-HMAs组的合并ORR较低（RR = 0.44，95%CI 0.28-0.69，P < 0.001），但OS无显著差异（HR = 1.30，95%CI 0.52-3.26，P = 0.58）。然而，仅有2项研究，结果应谨慎对待。在基于细胞遗传学风险、年龄和AML类型（初发、继发、治疗相关或既往有髓系疾病队列的治疗史）的其他亚组分析中，OS益处相似。