Achieving MRD negativity in AML: how important is this and how do we get there?

IF 2.9 3区 教育学 Q1 EDUCATION, SCIENTIFIC DISCIPLINES
Christopher S Hourigan
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引用次数: 7

Abstract

Multiple studies have demonstrated that patients with acute myeloid leukemia (AML) who have measurable residual disease (MRD) detected during or after treatment have higher relapse rates and worse survival than similar patients testing negative. Updated response criteria for AML reflect the understanding that achievement of complete remission (CR) with no detectable MRD using high-sensitivity tests represents a superior response over conventional cytomorphological CR alone. Potential use cases for AML MRD testing are diverse and include patient selection for clinical trials and therapeutic assignment, early relapse detection and intervention during sequential monitoring, and drug development, including deep quantification for antileukemia efficacy and as a surrogate endpoint for overall survival in regulatory approvals. Testing for AML MRD has not, however, been harmonized, and many technical and clinical questions remain. The implications of MRD test results for specific therapeutic combinations, molecular subsets, test types, treatment time points, sample types, and patient characteristics remain incompletely defined. No perfect AML MRD test or testing strategy currently exists, and the evidence basis for clinical recommendations in this rare disease is sparse but growing. It is unproven whether conversion of an MRD test result from positive to negative by additional therapeutic intervention improves relapse risk and survival. Several national- and international-level consortia have recently been initiated to advance the generation and collection of evidence to support the use of AML MRD testing in clinical practice, drug development, and regulatory approvals.

在AML中实现MRD阴性:这有多重要?我们如何实现这一目标?
多项研究表明,在治疗期间或治疗后检测到可测量残留疾病(MRD)的急性髓性白血病(AML)患者的复发率和生存率高于检测阴性的类似患者。AML的最新反应标准反映了这样一种认识,即使用高灵敏度试验实现完全缓解(CR)而未检测到MRD代表比单独使用常规细胞形态学CR更好的反应。AML MRD检测的潜在用例多种多样,包括临床试验和治疗分配的患者选择,顺序监测期间的早期复发检测和干预,以及药物开发,包括抗白血病疗效的深度量化,以及监管部门批准的总生存期的替代终点。然而,AML MRD的检测尚未统一,许多技术和临床问题仍然存在。MRD测试结果对特定治疗组合、分子亚群、测试类型、治疗时间点、样本类型和患者特征的含义仍然不完全确定。目前尚不存在完善的AML MRD检测或检测策略,临床推荐的证据基础较少,但在不断增长。目前尚不清楚通过额外的治疗干预是否可以将MRD检测结果从阳性转化为阴性,从而提高复发风险和生存率。最近已经启动了几个国家和国际层面的联盟,以推进证据的生成和收集,以支持在临床实践、药物开发和监管批准中使用AML MRD检测。
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来源期刊
Hematology. American Society of Hematology. Education Program
Hematology. American Society of Hematology. Education Program EDUCATION, SCIENTIFIC DISCIPLINES-HEMATOLOGY
CiteScore
4.70
自引率
3.30%
发文量
0
期刊介绍: Hematology, the ASH Education Program, is published annually by the American Society of Hematology (ASH) in one volume per year.
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