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Molecular MRD is strongly prognostic in patients with NPM1-mutated AML receiving venetoclax-based nonintensive therapy.

  • Othman, Jad1, 2, 3
  • Tiong, Ing S4, 5, 6
  • O'Nions, Jenny7
  • Dennis, Mike8
  • Mokretar, Katya9
  • Ivey, Adam5
  • Austin, Michael10
  • Latif, Anne-Louise11
  • Amer, Mariam12
  • Chan, Wei Yee7
  • Crawley, Charles13
  • Crolla, Francesca14
  • Cross, Joe15
  • Dang, Ray16
  • Elliot, Johnathon8
  • Fong, Chun Y6
  • Galli, Sofia17
  • Gallipoli, Paolo10
  • Hogan, Francesca18
  • Kalkur, Pallavi19
  • And 16 more
  • 1 Department of Medical and Molecular Genetics, King's College London, London, United Kingdom. , (United Kingdom)
  • 2 Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. , (United Kingdom)
  • 3 Faculty of Medicine and Health, University of Sydney, Sydney, Australia. , (Australia)
  • 4 Peter MacCallum Cancer Centre, Royal Melbourne Hospital and Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. , (Australia)
  • 5 Alfred Hospital and Monash University, Melbourne, Australia. , (Australia)
  • 6 Austin Health and Olivia Newton John Cancer Research Institute, Melbourne, Australia. , (Australia)
  • 7 Department of Haematology, University College London Hospital NHS Foundation Trust, London, United Kingdom. , (United Kingdom)
  • 8 The Christie NHS Foundation Trust, Manchester, United Kingdom. , (United Kingdom)
  • 9 Cancer Genetics, Synnovis, London, United Kingdom. , (United Kingdom)
  • 10 Barts Cancer Institute, Queen Mary University of London, London, United Kingdom. , (United Kingdom)
  • 11 Department of Haematology, Queen Elizabeth University Hospital, Glasgow, United Kingdom. , (United Kingdom)
  • 12 Haematology, University Hospital Southampton, Southampton, United Kingdom. , (United Kingdom)
  • 13 Department of Haematology, Addenbrooke's Hospital, Cambridge, United Kingdom. , (United Kingdom)
  • 14 Haematology, Musgrove Park Hospital, Taunton, United Kingdom. , (United Kingdom)
  • 15 Haematology Department, University Hospital Bristol, Bristol, United Kingdom. , (United Kingdom)
  • 16 James Cook University Hospital, Middlesbrough, United Kingdom. , (United Kingdom)
  • 17 Frimley Park Hospital, London, United Kingdom. , (United Kingdom)
  • 18 University Hospital of Wales, Cardiff, United Kingdom. , (United Kingdom)
  • 19 Southend Hospital, Southend, United Kingdom. , (United Kingdom)
  • 20 Department of Haematology, Leeds Teaching Hospitals Trust, Leeds, United Kingdom. , (United Kingdom)
  • 21 Department of Haematology, King's College Hospital, London, United Kingdom. , (United Kingdom)
  • 22 Worthing Hospital, Worthing, United Kingdom. , (United Kingdom)
  • 23 City Hospitals Sunderland NHS Trust, Sunderland, United Kingdom. , (United Kingdom)
  • 24 Centre for Clinical Haematology, University Hospitals Birmingham, Birmingham, United Kingdom. , (United Kingdom)
  • 25 Peterborough City Hospital, Peterborough, United Kingdom. , (United Kingdom)
  • 26 Royal Stoke University Hospital, University Hospital of North Midlands NHS Trust, Stoke-on-Trent, United Kingdom. , (United Kingdom)
  • 27 Nottingham University Hospital, Nottingham, United Kingdom. , (United Kingdom)
  • 28 Torbay Hospital, Torquay, United Kingdom. , (United Kingdom)
Published Article
American Society of Hematology
Publication Date
Jan 25, 2024
DOI: 10.1182/blood.2023021579
PMID: 37647641


Assessment of measurable residual disease (MRD) by quantitative reverse transcription polymerase chain reaction is strongly prognostic in patients with NPM1-mutated acute myeloid leukemia (AML) treated with intensive chemotherapy; however, there are no data regarding its utility in venetoclax-based nonintensive therapy, despite high efficacy in this genotype. We analyzed the prognostic impact of NPM1 MRD in an international real-world cohort of 76 previously untreated patients with NPM1-mutated AML who achieved complete remission (CR)/CR with incomplete hematological recovery following treatment with venetoclax and hypomethylating agents (HMAs) or low-dose cytarabine (LDAC). A total of 44 patients (58%) achieved bone marrow (BM) MRD negativity, and a further 14 (18%) achieved a reduction of ≥4 log10 from baseline as their best response, with no difference between HMAs and LDAC. The cumulative rates of BM MRD negativity by the end of cycles 2, 4, and 6 were 25%, 47%, and 50%, respectively. Patients achieving BM MRD negativity by the end of cycle 4 had 2-year overall of 84% compared with 46% if MRD was positive. On multivariable analyses, MRD negativity was the strongest prognostic factor. A total of 22 patients electively stopped therapy in BM MRD-negative remission after a median of 8 cycles, with 2-year treatment-free remission of 88%. In patients with NPM1-mutated AML attaining remission with venetoclax combination therapies, NPM1 MRD provides valuable prognostic information. © 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

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