Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study.
Adenine
/ analogs & derivatives
Aged
Aged, 80 and over
Chlorambucil
/ administration & dosage
Disease-Free Survival
Drug Administration Schedule
Female
Follow-Up Studies
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
/ drug therapy
Male
Patient Safety
Piperidines
Prognosis
Progression-Free Survival
Pyrazoles
/ administration & dosage
Pyrimidines
/ administration & dosage
Risk
Treatment Outcome
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
11
04
2019
accepted:
22
08
2019
revised:
08
08
2019
pubmed:
20
10
2019
medline:
25
8
2020
entrez:
20
10
2019
Statut:
ppublish
Résumé
RESONATE-2 is a phase 3 study of first-line ibrutinib versus chlorambucil in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients aged ≥65 years (n = 269) were randomized 1:1 to once-daily ibrutinib 420 mg continuously or chlorambucil 0.5-0.8 mg/kg for ≤12 cycles. With a median (range) follow-up of 60 months (0.1-66), progression-free survival (PFS) and overall survival (OS) benefits for ibrutinib versus chlorambucil were sustained (PFS estimates at 5 years: 70% vs 12%; HR [95% CI]: 0.146 [0.098-0.218]; OS estimates at 5 years: 83% vs 68%; HR [95% CI]: 0.450 [0.266-0.761]). Ibrutinib benefit was also consistent in patients with high prognostic risk (TP53 mutation, 11q deletion, and/or unmutated IGHV) (PFS: HR [95% CI]: 0.083 [0.047-0.145]; OS: HR [95% CI]: 0.366 [0.181-0.736]). Investigator-assessed overall response rate was 92% with ibrutinib (complete response, 30%; 11% at primary analysis). Common grade ≥3 adverse events (AEs) included neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), and hyponatremia (6%); occurrence of most events as well as discontinuations due to AEs decreased over time. Fifty-eight percent of patients continue to receive ibrutinib. Single-agent ibrutinib demonstrated sustained PFS and OS benefit versus chlorambucil and increased depth of response over time.
Identifiants
pubmed: 31628428
doi: 10.1038/s41375-019-0602-x
pii: 10.1038/s41375-019-0602-x
pmc: PMC7214263
mid: NIHMS1571598
doi:
Substances chimiques
Piperidines
0
Pyrazoles
0
Pyrimidines
0
Chlorambucil
18D0SL7309
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
787-798Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
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