Outcomes with ibrutinib by line of therapy and post-ibrutinib discontinuation in patients with chronic lymphocytic leukemia: Phase 3 analysis.
Journal
American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
19
10
2018
revised:
02
01
2019
accepted:
11
02
2019
pubmed:
16
2
2019
medline:
28
1
2020
entrez:
16
2
2019
Statut:
ppublish
Résumé
The efficacy of ibrutinib has been demonstrated in patients with chronic lymphocytic leukemia (CLL), including as first-line therapy. However, outcomes after ibrutinib discontinuation have previously been limited to higher-risk populations with relapsed/refractory (R/R) disease. The objective of this study was to evaluate outcomes of ibrutinib-treated patients based on prior lines of therapy, including after ibrutinib discontinuation. Data were analyzed from two multicenter phase 3 studies of single-agent ibrutinib: RESONATE (PCYC-1112) in patients with R/R CLL and RESONATE-2 (PCYC-1115) in patients with treatment-naive (TN) CLL without del(17p). This integrated analysis included 271 ibrutinib-treated non-del(17p) patients with CLL (136 TN and 135 R/R). Median progression-free survival (PFS) was not reached for subgroups with 0 and 1/2 prior therapies but was 40.6 months for patients with ≥3 therapies (median follow-up: TN, 36 months; R/R, 44 months). Median overall survival (OS) was not reached in any subgroup. Overall response rate (ORR) was 92% in TN and 92% in R/R, with depth of response increasing over time. Adverse events (AEs) and ibrutinib discontinuation due to AEs were similar between patient groups. Most patients (64%) remain on treatment. OS following discontinuation was 9.3 months in R/R patients (median follow-up 18 months, n = 51) and was not reached in TN patients (median follow-up 10 months, n = 30). In this integrated analysis, ibrutinib was associated with favorable PFS and OS, and high ORR regardless of prior therapies in patients with CLL. The best outcomes following ibrutinib discontinuation were for patients receiving ibrutinib in earlier lines of therapy.
Identifiants
pubmed: 30767298
doi: 10.1002/ajh.25436
pmc: PMC6593416
doi:
Substances chimiques
Piperidines
0
Pyrazoles
0
Pyrimidines
0
ibrutinib
1X70OSD4VX
Adenine
JAC85A2161
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
554-562Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : Janssen Pharmaceuticals
Pays : International
Organisme : Pharmacyclics LLC, an AbbVie Company
Pays : International
Informations de copyright
© 2019 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.
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