Postinduction molecular MRD identifies patients with NPM1 AML who benefit from allogeneic transplant in first remission

Othman, Jad, Potter, Nicola, Ivey, Adam, Jovanovic, Jelena, Runglall, Manohursingh, Freeman, Sylvie D., Gilkes, Amanda, Thomas, Ian, Johnson, Sean, Canham, Joanna ORCID: https://orcid.org/0000-0003-3482-0990, Cavenagh, Jamie, Kottaridis, Panagiotis, Arnold, Claire, Ommen, Hans Beier, Overgaard, Ulrik Malthe, Dennis, Mike, Burnett, Alan, Wilhelm-Benartzi, Charlotte, Dillon, Richard and Russell, Nigel H. 2024. Postinduction molecular MRD identifies patients with NPM1 AML who benefit from allogeneic transplant in first remission. Blood 143 (19) , pp. 1931-1936. 10.1182/blood.2023023096 Item availability restricted.

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Abstract

Abstract Selection of patients with NPM1-mutated acute myeloid leukemia (AML) for allogeneic transplant in first complete remission (CR1-allo) remains controversial because of a lack of robust data. Consequently, some centers consider baseline FLT3–internal tandem duplication (ITD) an indication for transplant, and others rely on measurable residual disease (MRD) status. Using prospective data from the United Kingdom National Cancer Research Institute AML17 and AML19 studies, we examined the impact of CR1-allo according to peripheral blood NPM1 MRD status measured by quantitative reverse transcription polymerase chain reaction after 2 courses of induction chemotherapy. Of 737 patients achieving remission, MRD was positive in 19%. CR1-allo was performed in 46% of MRD+ and 17% of MRD− patients. We observed significant heterogeneity of overall survival (OS) benefit from CR1-allo according to MRD status, with substantial OS advantage for MRD+ patients (3-year OS with CR1-allo vs without: 61% vs 24%; hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.24-0.64; P < .001) but no benefit for MRD− patients (3-year OS with CR1-allo vs without: 79% vs 82%; HR, 0.82; 95% CI, 0.50-1.33; P = .4). Restricting analysis to patients with coexisting FLT3-ITD, again CR1-allo only improved OS for MRD+ patients (3-year OS, 45% vs 18%; compared with 83% vs 76% if MRD-); no interaction with FLT3 allelic ratio was observed. Postinduction molecular MRD reliably identifies those patients who benefit from allogeneic transplant in first remission. The AML17 and AML19 trials were registered at www.isrctn.com as #ISRCTN55675535 and #ISRCTN78449203, respectively.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc-nd/4.0/, Start Date: 2025-05-09
Publisher:	American Society of Hematology (ASH Publications)
ISSN:	0006-4971
Date of First Compliant Deposit:	13 May 2024
Date of Acceptance:	23 January 2024
Last Modified:	13 May 2024 09:00
URI:	https://orca.cardiff.ac.uk/id/eprint/168870

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