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2021 Update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working Party

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Michael Heuser, Sylvie D. Freeman, Gert J. Ossenkoppele, Francesco Buccisano, Christopher S. Hourigan, Lok Lam Ngai, Jesse M. Tettero, Costa Bachas, Constance Baer, Marie Christine Béné, Veit Bücklein, Anna Czyz, Barbara Denys, Richard Dillon, Michaela Feuring-Buske, Monica L. Guzman, Torsten Haferlach, Lina Han, Julia K. Herzig, Jeffrey L. Jorgensen & 25 more Wolfgang Kern, Marina Y. Konopleva, Francis Lacombe, Marta Libura, Agata Majchrzak, Luca Maurillo, Yishai Ofran, Jan Philippe, Adriana Plesa, Claude Preudhomme, Farhad Ravandi, Christophe Roumier, Marion Subklewe, Felicitas Thol, Arjan A. van de Loosdrecht, Bert A. van der Reijden, Adriano Venditti, Agnieszka Wierzbowska, Peter J.M. Valk, Brent L. Wood, Roland B. Walter, Christian Thiede, Konstanze Döhner, Gail J. Roboz, Jacqueline Cloos

Original languageEnglish
Pages (from-to)2753-2767
Number of pages15
JournalBlood
Volume138
Issue number26
DOIs
Published30 Dec 2021

Bibliographical note

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

King's Authors

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.

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