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

•NPM1 MRD by qRT-PCR provides valuable prognostic information in patients with AML treated with venetoclax combinations.•Achievement of MRD negativity in the first 4 cycles identifies a group of patients with good outcomes. [Display omitted] Assessment of measurable residual disease (MRD) by quantit...

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Published in:Blood 2024-01, Vol.143 (4), p.336-341
Main Authors: Othman, Jad, Tiong, Ing S., O'Nions, Jenny, Dennis, Mike, Mokretar, Katya, Ivey, Adam, Austin, Michael, Latif, Anne-Louise, Amer, Mariam, Chan, Wei Yee, Crawley, Charles, Crolla, Francesca, Cross, Joe, Dang, Ray, Elliot, Johnathon, Fong, Chun Y., Galli, Sofia, Gallipoli, Paolo, Hogan, Francesca, Kalkur, Pallavi, Khan, Anjum, Krishnamurthy, Pramila, Laurie, John, Loo, Sun, Marshall, Scott, Mehta, Priyanka, Murthy, Vidhya, Nagumantry, Sateesh, Pillai, Srinivas, Potter, Nicola, Sellar, Rob, Taylor, Tom, Zhao, Rui, Russell, Nigel H., Wei, Andrew H., Dillon, Richard
Format: Article
Language:English
Subjects:
Bridged Bicyclo Compounds, Heterocyclic
Cytarabine
Humans
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - genetics
Mutation
Neoplasm, Residual - genetics
Nucleophosmin
Prognosis
Sulfonamides
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Summary:•NPM1 MRD by qRT-PCR provides valuable prognostic information in patients with AML treated with venetoclax combinations.•Achievement of MRD negativity in the first 4 cycles identifies a group of patients with good outcomes. [Display omitted] 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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.2023021579