Role of MRD testing in acute myeloid leukemias. What is the status and how to get there?

Abstract

Measurable residual disease (MRD) testing, high-sensitivity methods to estimate persistent leukemia below the threshold of conventional cytomorphological assessment, has the potential to transform the evaluation of treatment response, relapse prediction, and therapy development and selection for patients with acute myeloid leukemia (AML). Evidence accumulated over more than four decades demonstrates that patients testing MRD positive after treatment have substantially higher rates of relapse and inferior survival compared with those testing negative, but the heterogenous nature of the collection of diseases labeled as AML has resulted in slower clinical application and impact of such testing compared with other hematological malignancies. No single optimal universal AML MRD assay currently exists. The choice between imperfect AML MRD testing options requires explicit consideration of the evidence supporting a specific clinical context of use. Emerging technologies offer the prospect of improved sensitivity, specificity, and standardization, but most lack the prospective clinical validation required to guide practice change. Critically, beyond prognostication, it remains unproven in which clinical setting(s) therapeutic intervention guided by AML MRD results can improve overall survival. Updated clinical response criteria now recognize complete remission with MRD negativity as the optimal treatment response, and MRD status is increasingly integrated into clinical trial design, transplant decision-making, and drug development. Several large collaborative efforts, including prospective studies, are now generating the evidence needed to resolve fundamental questions in AML MRD regarding optimal assay selection, testing intervals, clinically meaningful thresholds, and surrogate endpoint validity. The coming years will determine whether AML MRD-guided therapy delivers measurable, patient-meaningful benefit.