Assessment of the Efficacy of Therapies Following Venetoclax Discontinuation in CLL Reveals BTK Inhibition as an Effective Strategy.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 07 2020
15 07 2020
Historique:
received:
23
11
2019
revised:
05
02
2020
accepted:
17
03
2020
pubmed:
22
3
2020
medline:
12
3
2021
entrez:
22
3
2020
Statut:
ppublish
Résumé
Venetoclax-based therapy is a standard-of-care option in first-line and relapsed/refractory chronic lymphocytic leukemia (CLL). Patient management following venetoclax discontinuation remains nonstandard and poorly understood. To address this, we conducted a large international study to identify a cohort of 326 patients who discontinued venetoclax and have been subsequently treated. Coprimary endpoints were overall response rate (ORR) and progression-free survival for the post-venetoclax treatments stratified by treatment type [Bruton's tyrosine kinase inhibitor (BTKi), PI3K inhibitor (PI3Ki), and cellular therapies]. We identified patients with CLL who discontinued venetoclax in the first-line (4%) and relapsed/refractory settings (96%). Patients received a median of three therapies prior to venetoclax; 40% were BTKi naïve ( For BTKi-naïve patients, selection of covalently binding BTKis results in high ORR and durable remissions. For BTKi-exposed patients, covalent BTK inhibition is not effective in the setting of BTKi resistance. PI3Kis following venetoclax do not appear to result in durable remissions. We conclude that BTKi in naïve or previously responsive patients and cellular therapies following venetoclax may be the most effective strategies.
Identifiants
pubmed: 32198151
pii: 1078-0432.CCR-19-3815
doi: 10.1158/1078-0432.CCR-19-3815
pmc: PMC8588795
mid: NIHMS1614086
doi:
Substances chimiques
Bridged Bicyclo Compounds, Heterocyclic
0
Protein Kinase Inhibitors
0
Pyrazoles
0
Pyrimidines
0
Sulfonamides
0
venetoclax
N54AIC43PW
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Comment
Langues
eng
Sous-ensembles de citation
IM
Pagination
3589-3596Subventions
Organisme : NCI NIH HHS
ID : K12 CA120780
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentOn
Informations de copyright
©2020 American Association for Cancer Research.
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