Outcomes of older patients with NPM1-mutated AML: current treatments and the promise of venetoclax-based regimens.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
14 04 2020
14 04 2020
Historique:
received:
20
11
2019
accepted:
19
02
2020
entrez:
7
4
2020
pubmed:
7
4
2020
medline:
15
5
2021
Statut:
ppublish
Résumé
Nucleophosmin-1 mutations (NPM1+) occur in ∼30% of acute myeloid leukemia (AML) patients. Although typically associated with favorable prognosis, the beneficial impact of NPM1+ decreases with increasing age in patients treated with standard intensive chemotherapy (IC) or hypomethylating agents (HMAs). This retrospective analysis compared outcomes of NPM1+ AML patients treated with 1 of 3 induction approaches: HMA plus BCL-2 inhibitor venetoclax (VEN), HMA, or IC therapy. Composite complete response (CRc: CR + CR with incomplete count recovery) was seen in 96% (27/28), 36% (17/47), and 89% (204/228) of HMA + VEN, HMA, and IC patients, respectively (HMA + VEN vs HMA, P < .001; HMA + VEN vs IC, P = .10). Older patients (age >65 years) treated with HMA + VEN, HMA, or IC had CR rates of 88%, 28%, and 56%, respectively (HMA + VEN vs HMA, P < .001; HMA + VEN vs IC, P = .01). Significant improvement in overall survival (OS) was seen in patients age >65 years treated with HMA + VEN vs HMA (not reached [NR] vs 0.4 years; P < .001) or IC (NR vs 0.93 years; P = .001). Older patients treated with HMA + VEN had OS of 80% after median 1-year follow-up, with estimated 2-year OS of 70%. In the multivariable Cox model analysis, HMA + VEN was associated with a 69% lower risk of death compared with IC (hazard ratio, 0.31; 95% confidence interval, 0.12-0.83; type I error-adjusted P = .038). HMA + VEN combinations demonstrated impressive results compared with traditional standard-of-care regimens in older patients with NPM1+ AML.
Identifiants
pubmed: 32251497
pii: S2473-9529(20)31392-6
doi: 10.1182/bloodadvances.2019001267
pmc: PMC7160266
doi:
Substances chimiques
Bridged Bicyclo Compounds, Heterocyclic
0
NPM1 protein, human
0
Nuclear Proteins
0
Sulfonamides
0
Nucleophosmin
117896-08-9
venetoclax
N54AIC43PW
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1311-1320Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Informations de copyright
© 2020 by The American Society of Hematology.
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