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

Othman, J; Tiong, IS; O&#39;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

Author(s): 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;
Details: Publication Year 2024-01-25,Volume 143,Issue #4,Page 336-341
Journal Title: Blood
Publication Type: Research article
Abstract: 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.
Publisher: American Society of Hematology
Keywords: Humans; Prognosis; *Nucleophosmin; Mutation; *Leukemia, Myeloid, Acute/drug therapy/genetics; Cytarabine; Neoplasm, Residual/genetics; *Sulfonamides; *Bridged Bicyclo Compounds, Heterocyclic
Department(s): Pathology; Clinical Haematology
Publisher's Version: https://doi.org/10.1182/blood.2023021579
Open Access at Publisher's Site: https://doi.org/10.1182/blood.2023021579
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-03-13 05:27:12

Last Modified: 2024-03-13 05:27:28