Measurable residual disease testing in acute myeloid leukemia: current state, foundational models, and tools for future development.

Abstract

Acute myeloid leukemia (AML) is a lethal and rapidly progressive hematologic malignancy with high rates of relapse and treatment refractoriness. Management of AML is complicated by biological heterogeneity in a disease that is broadly defined by the clonal expansion of myeloblasts that otherwise play an important role in healthy marrow tissues. While subtypes of AML are increasingly defined by druggable driver mutations including FLT3-ITD, IDH1, IDH2, and NPM1, conventional chemotherapy and reduced intensity induction regimens (e.g., azacitidine-venetoclax) remain therapeutic backbones. One area of active development for personalization of AML treatment is the assessment of measurable residual disease (MRD). MRD testing in AML is complicated by uncertainty regarding the physiologic compartment of persistent and relapsing myeloblasts, and by increasing recognition of myeloid driver mutations in some healthy bone marrow states, such as clonal hematopoiesis of indeterminate potential (CHIP). Even in large academic centers, MRD tools are not yet universally available. Standardized workflows for MRD implementation are only beginning to enter consensus and guideline documents. Current understanding of AML biology and state-of-the-art tools for MRD measurement are reviewed here in an effort to promote clinical and laboratory investigator collaboration for the development of reliable tools for improving outcomes in this deadly disease. Clinical trial number: not applicable.