Venetoclax in combination with nucleoside analogs in acute myelogenous leukemia.
Journal
Current opinion in oncology
ISSN: 1531-703X
Titre abrégé: Curr Opin Oncol
Pays: United States
ID NLM: 9007265
Informations de publication
Date de publication:
01 09 2022
01 09 2022
Historique:
pubmed:
21
7
2022
medline:
12
8
2022
entrez:
20
7
2022
Statut:
ppublish
Résumé
Venetoclax in combination with nucleoside analogs such as hypomethylating agents (HMA) and low-dose cytarabine (LDAC) has led to unprecedented response and survival outcomes in patients with acute myeloid leukemia (AML). This has spurred the development of regimens combining venetoclax with other nucleoside analogs with distinct mechanisms of action. Here, we review older and newer nucleoside analogs, the rationale for their combination with venetoclax, and clinical evidence for the combination when available. Venetoclax with HMA prolonged survival in a phase 3 study. Additionally, biologic correlates of response and resistance to venetoclax with HMA have been identified. The addition of venetoclax to standard intensive regimens containing higher doses of cytarabine and purine nucleoside analogs are safe and induce very high rates of remission and measurable residual disease negativity (MRD) negativity in newly diagnosed and relapsed/refractory AML. Investigational nucleoside analogs aim to improve upon the safety, bioavailability, or efficacy of approved venetoclax combinations and are currently being evaluated in clinical studies. The development of venetoclax with HMA has transformed care for elderly adults with AML and opened the door for novel combinations of venetoclax with other nucleoside analogs. Further clinical studies are needed to see if these novel combinations further improve outcomes in AML particularly for patients with high-risk disease.
Identifiants
pubmed: 35855507
doi: 10.1097/CCO.0000000000000868
pii: 00001622-202209000-00017
doi:
Substances chimiques
Bridged Bicyclo Compounds, Heterocyclic
0
Nucleosides
0
Sulfonamides
0
Cytarabine
04079A1RDZ
venetoclax
N54AIC43PW
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
531-539Subventions
Organisme : NCI NIH HHS
ID : K12 CA001727
Pays : United States
Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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