Advancing the Minimal Residual Disease Concept in Acute Myeloid Leukemia

Abstract

The criteria to evaluate response to treatment in acute myeloid leukemia (AML) have changed little in the past sixty years. It is now possible to use higher sensitivity tools to measure residual disease burden in AML. Such minimal or measurable residual disease (MRD) measurements provide a deeper understanding of current patient status and allow stratification for risk of subsequent clinical relapse. Despite these obvious advantages, and after over a decade of laboratory investigation and pre-clinical validation, MRD measurements are not currently routinely used for clinical decision-making or drug development in non-APL AML. We review here some potential constraints that may have delayed adoption including a natural hesitancy of end users, economic impact concerns, misperceptions regarding the meaning of and need for assay sensitivity, the lack of one single MRD solution for all AML patients and finally the need to involve patients in decision making based on such correlates. It is our opinion that none of these issues represent insurmountable barriers and our hope is that by providing potential solutions we can help map a path forward to a future where our patients will be offered personalized treatment plans based on the amount of AML they have left remaining to treat.

Bone marrow evaluation for diagnosis and monitoring of acute myeloid leukemia

“…The sensitivity of any particular MRD technique used is likely of lesser importance than issues of amount, type, and frequency of sampling; clonal heterogeneity and antigen drift; technical reproducibility; and interpretation and integration of such measurements into clinical care. 79,91 The sensitivities of multiple targets assessed by MFC or PCR, which range from 1:100 to 1:200,000, have been comprehensively summarized by Hokland et al 82 …”

Precision medicine for acute myeloid leukemia

“…Additionally, the clonal composition of residual leukemia during or after treatment may provide predictive information in the form of mutations, biology or phenotype known to be associated with response or resistance to a therapy or combination of therapy (as determined from the approaches described in the prior two sections) – to allow rational prophylaxis of relapse with those agents most likely like to be efficacious[16]. Many technical, logistical and behavioral challenges remain however to be overcome before AML “MRD” measurements are adopted as standard of care [17]…”

The Development of Personalized Medicine: Acute Myeloid Leukemia as a Model

“…6 Moreover, a baseline immunophenotypic result before treatment is important for treatment response evaluation and measurable residual disease (MRD) monitoring. [7][8][9] Cytogenetic and molecular analyses are also required for all newly-diagnosed AML to predict patient prognosis and guide treatment decision. 4 Besides, these genetic data are also used to further classified patients into different subtype according to WHO 2016 classification criteria.…”