期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/ijms24054790
关键词
AML; MRD; relapse; novel therapy; NPM1
Measurable residual disease (MRD) assessment plays an important role in prognostication and guiding treatment decisions in acute myeloid leukemia (AML). With the development of new therapeutics and the recent approval of NPM1 MRD as a regulatory endpoint, MRD-directed therapy and its potential application in clinical trials are being explored. This article reviews emerging molecular MRD markers, the impact of novel therapeutics on MRD endpoints, and the use of MRD as a predictive biomarker in guiding therapy in AML.
Measurable residual disease (MRD) assessment in acute myeloid leukemia (AML) has an established role in disease prognostication, particularly in guiding decisions for hematopoietic cell transplantation in first remission. Serial MRD assessment is now routinely recommended in the evaluation of treatment response and monitoring in AML by the European LeukemiaNet. The key question remains, however, if MRD in AML is clinically actionable or does MRD merely portend fate? With a series of new drug approvals since 2017, we now have more targeted and less toxic therapeutic options for the potential application of MRD-directed therapy. Recent approval of NPM1 MRD as a regulatory endpoint is also foreseen to drastically transform the clinical trial landscape such as biomarker-driven adaptive design. In this article, we will review (1) the emerging molecular MRD markers (such as non-DTA mutations, IDH1/2, and FLT3-ITD); (2) the impact of novel therapeutics on MRD endpoints; and (3) how MRD might be used as a predictive biomarker to guide therapy in AML beyond its prognostic role, which is the focus of two large collaborative trials: AMLM26 INTERCEPT (ACTRN12621000439842) and MyeloMATCH (NCT05564390).
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