2021 Update on measurable residual disease in acute myeloid leukaemia

May 2022 Clinical practice Jolien Blokken

Assessment of measurable residual disease (MRD) in acute myeloid leukaemia (AML) is challenging. Several technologies are available for MRD quantification, but the assays and reporting lack standardisation and comparability. The goal of the European LeukemiaNet (ELN) AML MRD expert panel was to update the previous consensus article and provide expert recommendations on different technologies and current clinical uses of MRD. 

KEY MESSAGE FOR CLINICAL PRACTICE

In the rapidly evolving field of MRD analysis in AML, it is of utmost importance to standardise all procedures (pre-analytical, analytical and post-analytical) in order to use the full potential of MRD results.

Measurable residual disease (MRD) is an important biomarker in acute myeloid leukaemia (AML) that is used for prognostic, predictive, monitoring, and efficacy-response assessments. The European LeukemiaNet (ELN) MRD Working Party evaluated standardisation and harmonisation of MRD in an ongoing manner and has updated the 2018 ELN MRD recommendations based on significant developments in the field. New and revised recommendations were established during in-person and online meetings, and a 2-stage Delphi poll was conducted to optimise consensus. All recommendations are graded by levels of evidence and agreement. Major changes include technical specifications for next-generation sequencing-based MRD testing and integrative assessments of MRD irrespective of technology. Other topics include use of MRD as a prognostic and surrogate endpoint for drug testing; selection of the technique, material, and appropriate time points for MRD assessment; and clinical implications of MRD assessment. In addition to technical recommendations for flow- and molecular-MRD analysis, MRD thresholds are provided and MRD responses are defined. Recommendations on reporting MRD results are described in detail. It is concluded that MRD assessment in AML is complex but clinically relevant, and standardised approaches to application, interpretation, technical conduct, and reporting are of critical importance.

DISCUSSION BY PROF. DR. JAN PHILIPPÉ (GHENT UNIVERSITY)

This article is part of the Editor’s Pick of Prof. Dr. Jan Philippé. In the Editor’s Pick, we provide a snapshot of pivotal studies published in recent issues of the most important international journals focusing on haematology. The selection of the study discussed here was made by Prof. Dr. Jan Philippé (Senior full professor, University Hospital Ghent/ University Ghent). In addition to the key highlights of the article, an expert opinion by Prof. Philippé is included.

Detection of MRD by any methodology during morphological remission after standard chemotherapy is a strong prognostic factor for subsequent relapse and shorter survival in patients with AML. MRD monitoring may have value in guiding postremission therapy and identifying early relapse and as a surrogate endpoint in clinical trials to accelerate development of novel regimens. MRD assessment in AML has elicited considerable interest from clinicians, patients, regulatory authorities, industry, and researchers, and guidance in harmonisation, refinement, and validation of MRD testing is needed.

Reference

Heuser M, Freeman SD, Ossenkoppele GJ, et al. 2021 Update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working Party. Blood 2021;138(26): 2753-67.

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