Abstract
Measurable residual disease (MRD) is an important biomarker in acute myeloid leukemia (AML) that is used for prognostic, predictive, monitoring, and efficacy-response assessments. The European LeukemiaNet (ELN) MRD Working Party evaluated standardization and harmonization 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 optimize 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 end point 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, we provide MRD thresholds and define MRD response, and detail how MRD results should be reported and combined if several techniques are used. MRD assessment in AML is complex and clinically relevant, and standardized approaches to application, interpretation, technical conduct, and reporting are of critical importance.
Original language | English |
---|---|
Pages (from-to) | 2753-2767 |
Number of pages | 15 |
Journal | Blood |
Volume | 138 |
Issue number | 26 |
DOIs | |
Publication status | Published - 30 Dec 2021 |
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In: Blood, Vol. 138, No. 26, 30.12.2021, p. 2753-2767.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - 2021 Update on MRD in acute myeloid leukemia
T2 - a consensus document from the European LeukemiaNet MRD Working Party
AU - Heuser, Michael
AU - Freeman, Sylvie D.
AU - Ossenkoppele, Gert J.
AU - Buccisano, Francesco
AU - Hourigan, Christopher S.
AU - Ngai, Lok Lam
AU - Tettero, Jesse M.
AU - Bachas, Costa
AU - Baer, Constance
AU - Béné, Marie Christine
AU - Bücklein, Veit
AU - Czyz, Anna
AU - Denys, Barbara
AU - Dillon, Richard
AU - Feuring-Buske, Michaela
AU - Guzman, Monica L.
AU - Haferlach, Torsten
AU - Han, Lina
AU - Herzig, Julia K.
AU - Jorgensen, Jeffrey L.
AU - Kern, Wolfgang
AU - Konopleva, Marina Y.
AU - Lacombe, Francis
AU - Libura, Marta
AU - Majchrzak, Agata
AU - Maurillo, Luca
AU - Ofran, Yishai
AU - Philippe, Jan
AU - Plesa, Adriana
AU - Preudhomme, Claude
AU - Ravandi, Farhad
AU - Roumier, Christophe
AU - Subklewe, Marion
AU - Thol, Felicitas
AU - van de Loosdrecht, Arjan A.
AU - van der Reijden, Bert A.
AU - Venditti, Adriano
AU - Wierzbowska, Agnieszka
AU - Valk, Peter J.M.
AU - Wood, Brent L.
AU - Walter, Roland B.
AU - Thiede, Christian
AU - Döhner, Konstanze
AU - Roboz, Gail J.
AU - Cloos, Jacqueline
N1 - Funding Information: Conflict-of-interest disclosure: M.H. serves an advisory role for Abbvie, BMS/Celgene, Daiichi Sankyo, Jazz Pharmaceuticals, Novartis, Pfizer, Roche, Tolremo; has received honoraria from Jazz Pharmaceuticals, Janssen, and Novartis; and has received research funding to his institution from Astellas, Bayer Pharma AG, BergenBio, Daiichi Sankyo, Jazz Pharmaceuticals, Karyopharm, Novartis, Pfizer, and Roche. S.D.F. is a Speaker Bureau member for Pfizer and Jazz Phamaceuticals. G.J.O. serves an advisory role for Novartis, Pfizer, BMS, Janssen, Celgene, AGIOS, Amgen, Gilead, Astellas, Roche, Jazz Pharmaceuticals, and Merus; serves as a consultant for Janssen, Celgene, and Roche; and receives research support to his institute from Novartis, Janssen, and Celgene. F.B. serves an advisory role and is a Speaker Bureau member for Novartis. C.S.H. receives research support for his institution from Sellas. C. Baer is employed by the MML Munich Leukemia Laboratory. V.B. serves an advisory role for Amgen, Gilead, and Pfizer, and has received research funding to his institution from Gilead, Celgene, and Novartis. R.D. serves an advisory role for Abbvie, Jazz Pharmacueticals, Menarini, Novartis, and Pfizer; receives research support to his institution from Abbvie, Amgen; is a consultant for Abbvie, Astellas, Jazz Pharmaceuticals, Pfizer; and is a Speaker Bureau member for Astellas, Jazz Pharmaceuticals, Novartis, and Pfizer. M.L.G. serves an advisory role for BridgeMedicines, SeqRx, and Epsilen Bio; and receives research funding from Cellectis, BridgeMedicines, and Daiichi Sankyo. T.H. is part owner of the MML Munich Leukemia Laboratory. W.K. is part owner of the MML Munich Leukemia Laboratory. M.Y.K. has received research grants to her institution from AbbVie, F. Hoffman La-Roche, Stemline Therapeutics, Forty-Seven, Eli Lilly, Cellectis, Calithera, Ablynx, Agios, Ascentage, Astra Zeneca, Reata Pharmaceutical, Rafael Pharmaceutical, Sanofi, Janssen, and Genentech; has received royalties paid to Reata Pharm; and has a patent licensed to Eli Lilly and one pending to Novartis. M.L. is a Speaker Bureau member at Novartis and Angelini. L.M. serves an advisory role for Abbvie, Janssen, Novartis, and BMS/Celgene. Y.O. serves an advisory role for Amgen, Pfizer, Abbvie, BMS, Astellas, and Janssen; and has received honoria from Abbvie, Novartis, Roche, Astellas, and Janssen. C.P. has received personal fees and travel/accommodations from Amgen, Janssen, Novartis, Bristol Meyer Scribb, Abbvie, and Astellas; has received grants, personal fees, and travel/accommodations from Celgene; has received grants from Merck; and has received travel and hotel accommodations from Innate Pharma, Ariad, and Daiichi Sakyo. F.R. has received research funding from BMS/Celgene, Amgen, Xencor, Syros, Taiho, Astex, Prelude, Biomea Fusion, Macrogenics, Hutchmed, and Abbvie; served as an advisor or received honoraria from BMS/Celgene, Novartis, Syros, Taiho, Jazz Pharmaceuticals, AstraZeneca, Agios, Abbvie, Amgen, and Xencor. M.S. serves an advisory role for Amgen, Celgene, Gilead, Janssen, Novartis, Pfizer, and Seattle Genetics; received research funding to her institution from Amgen, Gilead, Miltenyi Biotec, Morphosys, Roche, and Seattle Genetics; provided consultancy for Amgen, BMS, Celgene, Gilead, Pfizer, Novartis, and Roche; and is a Speaker Bureau member at Amgen, Celgene, Gilead, Janssen, and Pfizer. F.T. serves an advisory role for BMS/Celgene, Novartis, Abbvie Daichi, Astellas, and Pfizer, and has received research support for her institution from BMS/Cellgene and Novartis. A.A.v.d.L. serves an advisory role for BMS/Celgene, Amgen, Novartis, and Takeda, and has received research funding to his institute from Alexion. A.V. serves an advisory role for Novartis, Pfizer, Jazz Pharmaceuticals, Amgen, Abbvie, Gilead, Astellas, Incyte, and Janssen & Cylag; has received research funding to the Department of Biomedicine and Prevention, University Tor Vergata from Sandoz and Jazz Pharmaceuticals; and is a Speaker Bureau member for Pfizer. A.W. serves an advisory role for Amgen, Pfizer, Abbvie, BMS, Astellas, and Janssen; and has received honoria from Abbvie, Novartis, Roche, Astellas, and Janssen. B.L.W. has received honoraria from Amgen, Seattle Genetics, Abbvie, Janssen, Astellas Pharma, Roche Diagnostics, and Beckman Coulter; has served an advisory role for Sysmex; and has received a research grants to his institute from Novartis, Amgen, Seattle Genetics, Pfizer, Juno Therapeutics, BiolineRx, Biosight, Stemline Therapeutics, Janssen Oncology, Kite, a Gilead company, and Macrogenics. R.B.W. has received research grants to his institute from Agios, Amgen, Aptevo, Arog, BioLineRx, Celgene, ImmunoGen, Janssen, Jazz, Kura, MacroGenics, Pfizer, Selvita, and Stemline; has ownership interests in Amphivena; and serves an advisory role for Agios, Amgen, Amphivena, Aptevo, Astellas, BioLineRx, Boston Biomedical, Bristol Myers Squibb, Celgene, Genentech, GlaxoSmithKline, Janssen, Jazz, Kite, Kronos, MacroGenics, New Link Genetics, Pfizer, and Race. C.T. serves an advisory role for Jazz Pharmaceuticals, Novartis; has received honoraria from Jazz Pharmaceuticals, Janssen, Novartis, Astellas, Illumina, and Thermo Fisher Scientific; has received research funding to his institution from Novartis, Jazz Pharmaceuticals; and has ownership in AgenDix. K.D. serves an advisory role for Abbvie, BMS/Celgene, Daiichi Sankyo, Jazz Pharmaceuticals, Janssen, Novartis, and Roche; has received honoraria from BMS/Celgene, Daiichi Sankyo, Jazz Pharmaceuticals, Janssen, Novartis, and Roche; and has received research funding to her institution from Astellas, Agios, and Novartis. G.J.R. serves an advisory role for AbbVie, Actinium, Agios, Amgen, Astex, Astellas, AstraZeneca, Bayer, bluebird bio, Blueprint Medicines, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Glaxo SmithKline, Helsinn, Janssen, Jasper Therapeutics, Jazz Pharmaceuticals, and MEI Pharma; is the Independent Data Monitoring Committee (IDMC) Chair for Mesoblast, Novartis, Otsuka, Pfizer, Roche/Genentech, and Sandoz; is the Independent Review Committee (IRC) Chair for Takeda; and has received a research grants for her institute from Cellectis and Janssen. J.C. serves an advisory role for Novartis; has received research grants for her institution from Novartis, Merus, Takeda, Genentech, and BD Biosciences; and has received a royalty/license from Navigate and BD Biosciences. The remaining authors declare no competing financial interests. Funding Information: This work was supported, in part, by the Intramural Research Program, National Heart, Lung, and Blood Institute National Institutes of Health. Funding Information: The authors thank Ruediger Hehlmann for continuous generous support of the ELN AML MRD Working Party on behalf of the European LeukemiaNet. This work was supported, in part, by the Intramural Research Program, National Heart, Lung, and Blood Institute National Institutes of Health. Publisher Copyright: © 2021 American Society of Hematology
PY - 2021/12/30
Y1 - 2021/12/30
N2 - Measurable residual disease (MRD) is an important biomarker in acute myeloid leukemia (AML) that is used for prognostic, predictive, monitoring, and efficacy-response assessments. The European LeukemiaNet (ELN) MRD Working Party evaluated standardization and harmonization 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 optimize 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 end point 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, we provide MRD thresholds and define MRD response, and detail how MRD results should be reported and combined if several techniques are used. MRD assessment in AML is complex and clinically relevant, and standardized approaches to application, interpretation, technical conduct, and reporting are of critical importance.
AB - Measurable residual disease (MRD) is an important biomarker in acute myeloid leukemia (AML) that is used for prognostic, predictive, monitoring, and efficacy-response assessments. The European LeukemiaNet (ELN) MRD Working Party evaluated standardization and harmonization 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 optimize 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 end point 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, we provide MRD thresholds and define MRD response, and detail how MRD results should be reported and combined if several techniques are used. MRD assessment in AML is complex and clinically relevant, and standardized approaches to application, interpretation, technical conduct, and reporting are of critical importance.
UR - http://www.scopus.com/inward/record.url?scp=85121986560&partnerID=8YFLogxK
U2 - 10.1182/blood.2021013626
DO - 10.1182/blood.2021013626
M3 - Article
C2 - 34724563
AN - SCOPUS:85121986560
SN - 0006-4971
VL - 138
SP - 2753
EP - 2767
JO - Blood
JF - Blood
IS - 26
ER -