Efficacy and safety of FDA-approved IDH inhibitors in the treatment of IDH mutated acute myeloid leukemia: a systematic review and meta-analysis.

IF 5.7 2区 医学 Q1 Medicine
Xiu Chen, Hongyun Xing, Xiaolu Xie, Liqiu Kou, Jun Li, Yaling Li
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引用次数: 0

Abstract

Objective: To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML).

Methods: We used R software to conduct a meta-analysis of prospective clinical trials of IDH inhibitors in the treatment of IDH-mutated AML published in PubMed, Embase, Clinical Trials, Cochrane Library and Web of Science from inception to November 15th, 2022.

Results: A total of 1109 IDH-mutated AML patients from 10 articles (11 cohorts) were included in our meta-analysis. The CR rate, ORR rate, 2-year survival (OS) rate and 2-year event-free survival (EFS) rate of newly diagnosed IDH-mutated AML (715 patients) were 47%, 65%, 45% and 29%, respectively. The CR rate, ORR rate, 2-year OS rate, median OS and median EFS of relapsed or refractory (R/R) IDH-mutated AML (394 patients) were 21%, 40%, 15%, 8.21 months and 4.73 months, respectively. Gastrointestinal adverse events were the most frequently occurring all-grade adverse events and hematologic adverse events were the most frequently occurring ≥ grade 3 adverse events.

Conclusion: IDH inhibitor is a promising treatment for R/R AML patients with IDH mutations. For patients with newly diagnosed IDH-mutated AML, IDH inhibitors may not be optimal therapeutic agents due to low CR rates. The safety of IDH inhibitors is controllable, but physicians should always pay attention to and manage the differentiation syndrome adverse events caused by IDH inhibitors. The above conclusions need more large samples and high-quality RCTs in the future to verify.

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FDA批准的IDH抑制剂治疗IDH突变急性髓性白血病的疗效和安全性:系统综述和荟萃分析。
目的系统评估FDA批准的异柠檬酸脱氢酶(IDH)抑制剂治疗IDH突变急性髓性白血病(AML)的疗效和安全性:我们使用R软件对PubMed、Embase、Clinical Trials、Cochrane Library和Web of Science上发表的从开始到2022年11月15日IDH抑制剂治疗IDH突变AML的前瞻性临床试验进行了荟萃分析:荟萃分析共纳入了10篇文章(11个队列)中的1109例IDH突变AML患者。新诊断的IDH突变型AML患者(715例)的CR率、ORR率、2年生存率(OS)和2年无事件生存率(EFS)分别为47%、65%、45%和29%。复发或难治性(R/R)IDH突变型AML(394名患者)的CR率、ORR率、2年OS率、中位OS和中位EFS分别为21%、40%、15%、8.21个月和4.73个月。胃肠道不良事件是最常发生的所有级别不良事件,血液学不良事件是最常发生的≥3级不良事件:结论:IDH抑制剂是治疗IDH突变的R/R急性髓细胞白血病患者的一种很有前景的方法。对于新诊断的IDH突变急性髓细胞白血病患者,由于CR率较低,IDH抑制剂可能不是最佳治疗药物。IDH抑制剂的安全性是可控的,但医生应时刻关注和处理IDH抑制剂引起的分化综合征不良事件。上述结论需要未来更多的大样本和高质量的RCT来验证。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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