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Venetoclax-based low intensity therapy in molecular failure of NPM1 mutated AML

Jimenez-Chillon, Carlos, Othman, Jad, Taussig, David, Jimenez-Vicente, Carlos, Martinez-Roca, Alexandra, Tiong, Ing Soo, Jain, Manish, Aries, James, Cakmak, Seda, Knapper, Steven ORCID:, Kristensen, Daniel Tuyet, Murthy, Vidhya, Galani, Joy Zacharoula, Kallmeyer, Charlotte, Ngu, Loretta, Veale, David, Bolam, Simon, Orfali, Nina, Parker, Anne, Manson, Cara, Parker, Jane, Erblich, Thomas, Richardson, Deborah, Mokretar, Katya, Potter, Nicola, Overgaard, Ulrik Malthe, Roug, Anne Stidsholt, Wei, Andrew H., Esteve, Jordi, Jädersten, Martin, Russell, Nigel and Dillon, Richard 2024. Venetoclax-based low intensity therapy in molecular failure of NPM1 mutated AML. Blood Advances 8 (2) , pp. 343-352. 10.1182/bloodadvances.2023011106

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Molecular failure in NPM1 mutated AML inevitably progresses to frank relapse if untreated. Recently published small case series show that venetoclax combined with low dose cytarabine or azacitidine can reduce or eliminate measurable residual disease (MRD). Here we report an international multicentre cohort of 79 patients treated for molecular failure with venetoclax combinations and report an overall molecular response (≥1-log reduction in MRD) in 66/79 (84%) and MRD negativity in 56/79 (71%). 18/79 (23%) patients required hospitalisation and no deaths were reported during treatment. 41 patients were bridged to allogeneic transplant with no further therapy and 25/41 were MRD negative assessed by RT-qPCR before transplant. Overall survival (OS) for the whole cohort at 2 years was 67%, event-free survival (EFS) was 45% and in responding patients there was no difference in survival in those who received a transplant using time-dependent analysis. Presence of FLT3-ITD mutation was associated with a lower response rate (64 vs. 91%, p<0.01), worse OS (HR 2.50, 95% CI 1.06-5.86, p=0.036) and EFS (HR 1.87, 95% CI 1.06-3.28, p=0.03). 18/35 non-transplanted patients became MRD negative and stopped treatment after a median of 10 months, with 2-year molecular relapse free survival of 62% from the end of treatment. Venetoclax based low intensive chemotherapy is a potentially effective treatment for molecular relapse in NPM1 mutated AML, either as a bridge to transplant or as definitive therapy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: License information from Publisher: LICENSE 1: URL:, Start Date: 2023-12-01
Publisher: American Society of Hematology
ISSN: 2473-9529
Date of First Compliant Deposit: 21 February 2024
Date of Acceptance: 6 November 2023
Last Modified: 27 Mar 2024 14:51

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