The minimal that kills: Why defining and targeting measurable residual disease is the Sine Qua Non for further progress in management of acute myeloid leukemia

Patients with acute myeloid leukemia (AML) who achieve morphologic remission in the bone marrow after initial treatment often continue to harbor residual leukemic cells that can give rise to disease relapse. Achievement of a deeper remission has been associated with a reduced risk of relapse and improved event-free and overall survival in several studies. However, standardization of diagnostic techniques, sample acquisition and test timing are needed before minimal, also known as measurable, residual disease (MRD) quantification can be used to guide treatment decision making. Furthermore, clinical trial evidence that preemptive intervention at MRD level can alter the natural history of AML is required. Herein, we outline the current landscape of MRD assessment in AML, summarize the available evidence and challenges, and highlight the potential for MRD status to serve as a surrogate endpoint for hard clinical outcomes and as an approvable endpoint in clinical trials for regulatory purposes.