Clinical outcomes of older patients with NPM1 -mutated or KMT2A- rearranged AML before menin inhibitors: a Beat AML report
Year: 2026
Type: article
Abstract: TO THE EDITOR: The treatment landscape of acute myeloid leukemia (AML) has advanced considerably in the past decade with the advent of novel small molecule inhibitors targeting mutations such as FLT3, IDH1/2, and, most recently, NPM1 and KMT2A rearrangements (KMT2A-r), moving toward an individualized, precision-based treatment approach. Menin inhibitors are an emerging class of targeted agents for the treatment of NPM1-mutated (NPM1-m) and KMT2A-r AML through disruption of leukemogenic transcription factor interactions. Revumenib, a first-in-class menin inhibitor, gained US Food and Drug Administration approval for relapsed/refractory KMT2A-r acute leukemias and NPM1-m AML based on the AUGMENT-101 trial, demonstrating composite remission rates (CRc) of 44% and 29.7%, respectively. Ziftomenib is also approved for relapsed/refractory NPM1-m AML, with a CRc of 26%. A Beat AML substudy investigated azacitidine and venetoclax (AZA/VEN) and revumenib in newly diagnosed older patients (aged >60 years) with NPM1-m or KMT2A-r AML, with a CRc of 81.4%. Given these findings, ongoing randomized studies are investigating AZA/VEN with menin inhibitor/placebo for newly diagnosed NPM1-m or KMT2A-r AML. However, there are limited historical data on outcomes in patients with NPM1-m and KMT2A-r in the modern era, particularly older patients receiving nonintensive therapies (NIT) such as hypomethylating agents (HMA) with or without VEN (HMA/VEN).
Source: Blood Advances
Authors: Joshua F. Zeidner, Jayanshu Jain, Rina Li Welkie, Ying Huang, Ronan T. Swords, Elie Traer, Eytan M. Stein, Tara L. Lin, Yazan F. Madanat, Robert H. Collins, Maria R. Baer, Vu H. Duong, William G. Blum, Martha L. Arellano, Wendy Stock, Olatoyosi Odenike, Rebecca L. Olin, Catherine C. Smith, James M. Foran, Gary J. Schiller, Emily K. Curran, Shivani Handa, Nyla A. Heerema, Timothy Chen, Molly Martycz, Mona Stefanos, Sonja G. Marcus, Leonard Rosenberg, Brian J. Druker, Ross L. Levine, Amy Burd, Ashley O. Yocum, Alice S. Mims, John C. Byrd, Uma Borate
Institutions: University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, The Ohio State University, Oregon Health & Science University, OHSU Knight Cancer Institute, Memorial Sloan Kettering Cancer Center, University of Kansas Medical Center, The University of Texas Southwestern Medical Center, University of Maryland, Baltimore, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Winship Cancer Institute, University of Chicago, University of California, San Francisco, Mayo Clinic in Florida, University of California, Los Angeles, University of Cincinnati
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
Funders: European High Performance Computing Joint Undertaking, Ministry of Health, Ontario, International Centre for Advanced Materials, National Science Foundation, Alfred P. Sloan Foundation, Gordon and Betty Moore Foundation, American Heart Association, Pfizer, Alexander von Humboldt-Stiftung, University of Michigan, Fondazione Cassa di Risparmio di Padova e Rovigo, University of Utah, Japan Agency for Medical Research and Development, Jürgen Manchot Stiftung, Jazz Pharmaceuticals, Comunidad de Madrid, UK Research and Innovation, MathWorks, Innovative Research Group Project of the National Natural Science Foundation of China, Japanese Society of Hematology, Syndax Pharmaceuticals, Universidad San Jorge, Royal Society of Chemistry, University College London, University of Oxford, European Commission, University of Edinburgh, University College Dublin, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Swedish Foundation for International Cooperation in Research and Higher Education, Danmarks Grundforskningsfond, National Natural Science Foundation of China, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Bundesministerium für Bildung und Forschung, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, University of Toronto, Conselho Nacional de Desenvolvimento Científico e Tecnológico, National Research Foundation of Korea, Magyar Tudományos Akadémia, Ministry of Agriculture, Forestry and Fisheries, Vetenskapsrådet, Thüringer Aufbaubank, Ministerio de Ciencia e Innovación, Shanghai Jiao Tong University, Fundação de Amparo à Pesquisa do Estado de Goiás, Alexander S. Onassis Public Benefit Foundation, Kungliga Fysiografiska Sällskapet i Lund, Einstein Stiftung Berlin, National Center for Geriatrics and Gerontology, Shanghai Hospital Development Center, Yunnan Provincial Science and Technology Department, Novo Nordisk Fonden, Gobierno de Aragón, Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, Servier, Swedish Orphan Biovitrum, Shanghai Rising-Star Program, Ministry of Science and ICT, South Korea, Region Uppsala, Shanghai Clinical Research Center, Natural Science Foundation of Sichuan Province, Ruijin Hospital, Agencia Nacional de Investigación y Desarrollo, National Institutes of Health, Animal and Plant Health Inspection Service, Horizon 2020 Framework Programme, Center for High Performance Computing, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Science and Technology Facilities Council, Christ's College, University of Cambridge, Churchill College, University of Cambridge, Australian Research Council, National Health and Medical Research Council, Japan Society for the Promotion of Science, Consejo Superior de Investigaciones Científicas, School of Medicine, Shanghai Jiao Tong University, Agencia Estatal de Investigación, National Key Research and Development Program of China, Key Science and Technology Program of Shaanxi Province, Vicerrectoría de Investigación y Extensión, Universidad Industrial de Santander, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Institute of Child Health and Human Development, Division of Information and Intelligent Systems, Division of Chemistry, Division of Biological Infrastructure, National Center for Advancing Translational Sciences, Hydrogen and Fuel Cell Technologies Office, Fondo Nacional de Desarrollo Científico y Tecnológico, Fondo de Fomento al Desarrollo Científico y Tecnológico, Daiichi Sankyo Europe, H2020 European Research Council, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Institute of Biomedicine, University of Turku, Ministry of Long-Term Care, North Carolina Policy Collaboratory, Intramural Research Program
OpenAlex ID: W7127420262