Venetoclax-based low intensity therapy in molecular failure of NPM1-mutated AML
Details
Publication Year 2024-01-23,Volume 8,Issue #2,Page 343-352
Journal Title
Blood Advances
Publication Type
Research article
Abstract
Molecular failure in NPM1-mutated acute myeloid leukemia (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 on an international multicenter cohort of 79 patients treated for molecular failure with venetoclax combinations and report an overall molecular response (≥1-log reduction in MRD) in 66 patients (84%) and MRD negativity in 56 (71%). Eighteen of 79 patients (23%) required hospitalization, and no deaths were reported during treatment. Forty-one patients were bridged to allogeneic transplant with no further therapy, and 25 of 41 were MRD negative assessed by reverse transcription quantitative polymerase chain reaction 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 < .01), worse OS (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.06-5.86; P = .036), and EFS (HR, 1.87; 95% CI, 1.06-3.28; P = .03). Eighteen of 35 patients who did not undergo transplant 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.
Publisher
American Society of Hematology
Keywords
Humans; *Nuclear Proteins/genetics; Nucleophosmin; Mutation; *Leukemia, Myeloid, Acute/drug therapy/genetics; Recurrence; *Sulfonamides; *Bridged Bicyclo Compounds, Heterocyclic
Department(s)
Pathology
Open Access at Publisher's Site
10.1182/bloodadvances.2023011106
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2024-02-13 06:41:42
Last Modified: 2024-02-22 12:36:31

© 2024 The Walter and Eliza Hall Institute of Medical Research. Access to this website is subject to our Privacy Policy and Terms of Use

An error has occurred. This application may no longer respond until reloaded. Reload 🗙