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Minimal residual disease

Measurable residual disease as a biomarker in acute myeloid leukemia: theoretical and practical considerations

Leukemia volume 35, pages 1529–1538 (2021)Cite this article

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Abstract

Several methodologies that rely on the detection of immunophenotypic or molecular abnormalities of the neoplastic cells are now available to quantify measurable (“minimal”) residual disease (MRD) in acute myeloid leukemia (AML). Although the perfect MRD test does not (yet) exist, the strong association between MRD and adverse patient outcomes has provided the impetus to use measures of MRD as biomarker in the routine care of AML patients and during clinical trials. MRD test results may inform the selection of postremission therapy in some patients but evidence supporting the use of MRD as predictive biomarker is still limited. Several retrospective studies have shown that conversion from undetectable to detectable MRD or increasing MRD over time is associated with overt disease recurrence, and MRD testing may therefore be valuable as a monitoring biomarker for early detection of relapse. Interpreting serial MRD data is complex, with open questions regarding the optimal timing and frequency of testing, as well as the identification of test-specific thresholds to define relapse. Importantly, it is unknown whether intervening at the time of MRD detection, rather than at overt disease recurrence, improves outcomes. Finally, using MRD as a surrogate efficacy-response biomarker to accelerate drug development/approval has already been accepted by regulatory authorities in other diseases and is of great interest as a potential strategy in AML. While the prognostic value of MRD in AML is well established, data from prospective clinical trials confirming that treatment effects on MRD directly relate to clinical outcomes are needed to further establish the role of MRD as a surrogate endpoint in AML.

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Acknowledgements

This research was supported in part by the Intramural Research Program of the National Heart, Lung, and Blood Institute of the National Institutes of Health.

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Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Roland B. Walter

  2. Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA

    Roland B. Walter

  3. Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA

    Roland B. Walter

  4. Department of Epidemiology, University of Washington, Seattle, WA, USA

    Roland B. Walter

  5. Department of Hematology, Sharee Zedeq Medical Center, Jerusalem, Israel

    Yishai Ofran

  6. Department of Hematology, Medical University of Lodz, Lodz, Poland

    Agnieszka Wierzbowska

  7. Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Farhad Ravandi

  8. Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    Christopher S. Hourigan

  9. Department of Hematology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands

    Lok Lam Ngai & Gert J. Ossenkoppele

  10. Department of Biomedicine and Prevention, Hematology, University Tor Vergata, Rome, Italy

    Adriano Venditti & Francesco Buccisano

  11. Hematology and Oncology, Weill Cornell Medicine and NewYork-Presbyterian Hospital, Cornell University, New York, NY, USA

    Gail J. Roboz

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Walter, R.B., Ofran, Y., Wierzbowska, A. et al. Measurable residual disease as a biomarker in acute myeloid leukemia: theoretical and practical considerations. Leukemia 35, 1529–1538 (2021). https://doi.org/10.1038/s41375-021-01230-4

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