Molecular MRD is strongly prognostic in patients with NPM1-mutated AML receiving venetoclax-based nonintensive therapy.
Author
Othman, JadTiong, 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
Publication date
2023-08-30
Metadata
Show full item recordAbstract
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.Citation
Othman J, Tiong IS, O'Nions J, Dennis M, Mokretar K, Ivey A, Austin M, Latif AL, Amer M, Chan WY, Crawley C, Crolla F, Cross J, Dang R, Elliot J, Fong CY, Galli S, Gallipoli P, Hogan F, Kalkur P, Khan A, Krishnamurthy P, Laurie J, Loo S, Marshall S, Mehta P, Murthy V, Nagumantry S, Pillai S, Potter N, Sellar R, Taylor T, Zhao R, Russell NH, Wei AH, Dillon R. Molecular MRD is strongly prognostic in patients with NPM1-mutated AML receiving venetoclax-based nonintensive therapy. Blood. 2024 Jan 25;143(4):336-341. doi: 10.1182/blood.2023021579.Type
ArticleAdditional Links
https://www.sciencedirect.com/journal/bloodPMID
37647641Journal
BloodPublisher
Elsevierae974a485f413a2113503eed53cd6c53
10.1182/blood.2023021579