TY - JOUR
T1 - Measurable residual disease as a biomarker in acute myeloid leukemia
T2 - theoretical and practical considerations
AU - Walter, Roland B.
AU - Ofran, Yishai
AU - Wierzbowska, Agnieszka
AU - Ravandi, Farhad
AU - Hourigan, Christopher S.
AU - Ngai, Lok Lam
AU - Venditti, Adriano
AU - Buccisano, Francesco
AU - Ossenkoppele, Gert J.
AU - Roboz, Gail J.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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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U2 - 10.1038/s41375-021-01230-4
DO - 10.1038/s41375-021-01230-4
M3 - Review article
C2 - 33758317
AN - SCOPUS:85103179905
SN - 0887-6924
VL - 35
SP - 1529
EP - 1538
JO - Leukemia
JF - Leukemia
IS - 6
ER -