Measurable residual disease as an actionable biomarker in acute myeloid leukemia. Ready or not?

Measurable residual disease (MRD) is a reliable biomarker measuring the quality of morphological complete remission in acute myeloid leukemia (AML). This review will illustrate the settings where, along with drug development, MRD monitoring is by itself an actionable therapeutic target and represents not only a prognostic marker but a predictive marker of response, prompting a further relevant progress toward personalized medicine.

The double nature of certain biomarkers (e.g. PML/RARA , bcr/abl , FLT3 , IDH1/2 , NPM1 ), useful for MRD monitoring and key actors in AML development, has emerged. The use of targeted drugs (e.g. FLT3 inhibitors, IDH1/2 inhibitors) or drug combination that are particularly active in specific AML subsets (e.g. Azacytidine/Venetoclax in NPM1 mutated AML), has paved the way to clinical trial experimenting maintenance or preemptive treatment driven by MRD persistence or reappearance.

Accurate and specific MRD monitoring, coupled with the increasing development of targeted drugs, will give to clinicians an extraordinary opportunity to anticipate the treatment of AML relapse in the early phases eventually increasing drug efficacy and long-term outcome of the patients (visual abstract).