Measurable residual disease monitoring in patients with acute myeloid leukemia treated with lower‐intensity therapy: Roadmap from an ELN‐DAVID expert panel

Abstract

With the availability of effective targeted agents, significant changes have occurred in the management of patients with acute myeloid leukemia (AML) over the past several years, particularly for those considered unfit for intensive chemotherapy. While testing for measurable residual disease (MRD) is now routinely performed in patients treated with intensive chemotherapy to refine prognosis and, possibly, inform treatment decision‐making, its value in the context of lower‐intensity regimens is unclear. As such regimens have gained in popularity and can be associated with higher response rates, the need to better define the role of MRD assessment and the appropriate time points and assays used for this purpose has increased. This report outlines a roadmap for MRD testing in patients with AML treated with lower‐intensity regimens. Experts from the European LeukemiaNet (ELN)–DAVID AML MRD working group reviewed all available data to propose a framework for MRD testing in future trials and clinical practice. A Delphi poll served to optimize consensus. Establishment of uniform standards for MRD assessments in lower‐intensity regimens used in treating patients with AML is clinically relevant and important for optimizing testing and, ultimately, improving treatment outcomes of these patients.

Measurable Residual Disease Detection in Acute Myeloid Leukemia: Current Challenges and Future Directions

“…Furthermore, the establishment of an LAIP by flow cytometry before the start of low intensity treatment is recommended. The recommended time points of MRD measurements of BM in low intensity treated patients include assessments after the first, second, fourth, and seventh cycle [24]. The results conclusively show that attaining complete MRD-negative remission in AML patients receiving VEN-based combinations is clearly linked to improved survival.…”

“…As NPM1 is regarded as a leukemia-specific mutation, falsely positive MRD results could lead to unnecessary treatment [ 23 ]. Therefore, current efforts undertaken by groups, such as the ELN–DAVID MRD Working Group, focus on standardization and quality control of qPCR-based MRD assays to generate comparable MRD results [ 24 ].…”

“…Furthermore, the establishment of an LAIP by flow cytometry before the start of low intensity treatment is recommended. The recommended time points of MRD measurements of BM in low intensity treated patients include assessments after the first, second, fourth, and seventh cycle [ 24 ].…”

AML in the elderly—A global view

“…52 Thus, for an elderly patient such as the present one, it would seem counterintuitive to be subjected to an allo-SCT, unless preceded by MRD measurements for which there are recommendations now for intensive 15 and lower-intensity therapy. 53 The overall answers of the five centres are surprisingly identical, probably because of long-term adherence to the ELN 2017 and 2022 recommendations. Does this mean that we can lean back and be satisfied with the global progress made in the treatment of AML?…”

Minimal residual disease monitoring in acute myeloid leukemia: Focus on MFC‐MRD and treatment guidance for elderly patients

“…The utilization of PB for MRD assessment in patients undergoing low-intensity therapy requires further validation. 13,34…”