Genetic risk stratification and outcomes among treatment-naive patients with AML treated with venetoclax and azacitidine
- Author(s)
- Döhner, H; Pratz, KW; DiNardo, CD; Wei, AH; Jonas, BA; Pullarkat, VA; Thirman, MJ; Récher, C; Schuh, AC; Babu, S; Li, X; Ku, G; Liu, Z; Sun, Y; Potluri, J; Dail, M; Chyla, B; Pollyea, DA;
- Details
- Publication Year 2024-11-21,Volume 144,Issue #21,Page 2211-2222
- Journal Title
- Blood
- Publication Type
- Research article
- Abstract
- The European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to the 2017 and 2022 ELN risk classifications and derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on overall survival (OS). Overall, 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. The ELN 2017 or 2022 prognostic criteria classified most patients as adverse-risk AML (60.2% and 72.8% for venetoclax-azacitidine and 65.5% and 75.2% for placebo-azacitidine, respectively). Although outcomes with venetoclax-azacitidine improved across all ELN risk groups compared with placebo-azacitidine, ELN classification systems poorly discriminated venetoclax-azacitidine outcomes. By applying a bioinformatic algorithm, new molecular signatures were derived differentiating OS outcomes with venetoclax-azacitidine. The mutational status of TP53, FLT3 internal tandem duplication (FLT3-ITD), NRAS, and KRAS categorized patients into higher-, intermediate-, and lower-benefit groups (52%, 25%, and 23% of patients, respectively), each associated with a distinct median OS (26.5 months [95% confidence interval (CI), 20.2-32.7]; 12.1 months [95% CI, 7.3-15.2]; and 5.5 months [95% CI, 2.8-7.6], respectively). ELN prognostic classifiers did not provide clinically meaningful risk stratification of OS outcomes in patients treated with venetoclax-azacitidine. TP53, FLT3-ITD, NRAS, and KRAS mutation status allows the classification of these patients into 3 risk groups with distinct differences in median OS. These trials were registered at www.clinicaltrials.gov as #NCT02993523 and #NCT02203773.
- Publisher
- American Society of Hematology
- Keywords
- Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use; *Azacitidine/therapeutic use/administration & dosage; *Bridged Bicyclo Compounds, Heterocyclic/therapeutic use/administration & dosage; *Leukemia, Myeloid, Acute/drug therapy/genetics/mortality; Mutation; Prognosis; Risk Assessment; *Sulfonamides/therapeutic use/administration & dosage; Treatment Outcome; Clinical Trials, Phase III as Topic; Clinical Trials, Phase I as Topic; Randomized Controlled Trials as Topic
- Department(s)
- Haematology
- Publisher's Version
- https://doi.org/10.1182/blood.2024024944
- Open Access at Publisher's Site
https://doi.org/10.1182/blood.2024024944- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-12-10 07:11:40
Last Modified: 2024-12-10 07:11:53