Final analysis from RESONATE: Up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma.
Adenine
/ analogs & derivatives
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ therapeutic use
Antineoplastic Agents, Immunological
/ therapeutic use
Cardiovascular Diseases
/ chemically induced
Female
Follow-Up Studies
Hematologic Diseases
/ chemically induced
Humans
Infections
/ etiology
Kaplan-Meier Estimate
Leukemia, Lymphocytic, Chronic, B-Cell
/ drug therapy
Male
Middle Aged
Piperidines
Progression-Free Survival
Protein Kinase Inhibitors
/ adverse effects
Pyrazoles
/ adverse effects
Pyrimidines
/ adverse effects
Remission Induction
Risk
Salvage Therapy
Treatment Outcome
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:
12 2019
12 2019
Historique:
received:
17
06
2019
revised:
03
09
2019
accepted:
09
09
2019
pubmed:
13
9
2019
medline:
14
4
2020
entrez:
13
9
2019
Statut:
ppublish
Résumé
Ibrutinib, a once-daily oral inhibitor of Bruton's tyrosine kinase, is approved in the United States and Europe for treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The phase 3 RESONATE study showed improved efficacy of single-agent ibrutinib over ofatumumab in patients with relapsed/refractory CLL/SLL, including those with high-risk features. Here we report the final analysis from RESONATE with median follow-up on study of 65.3 months (range, 0.3-71.6) in the ibrutinib arm. Median progression-free survival (PFS) remained significantly longer for patients randomized to ibrutinib vs ofatumumab (44.1 vs 8.1 months; hazard ratio [HR]: 0.148; 95% confidence interval [CI]: 0.113-0.196; P˂.001). The PFS benefit with ibrutinib vs ofatumumab was preserved in the genomic high-risk population with del(17p), TP53 mutation, del(11q), and/or unmutated IGHV status (median PFS 44.1 vs 8.0 months; HR: 0.110; 95% CI: 0.080-0.152), which represented 82% of patients. Overall response rate with ibrutinib was 91% (complete response/complete response with incomplete bone marrow recovery, 11%). Overall survival, censored for crossover, was better with ibrutinib than ofatumumab (HR: 0.639; 95% CI: 0.418-0.975). With up to 71 months (median 41 months) of ibrutinib therapy, the safety profile remained consistent with prior reports; cumulatively, all-grade (grade ≥3) hypertension and atrial fibrillation occurred in 21% (9%) and 12% (6%) of patients, respectively. Only 16% discontinued ibrutinib because of adverse events (AEs). These long-term results confirm the robust efficacy of ibrutinib in relapsed/refractory CLL/SLL irrespective of high-risk clinical or genomic features, with no unexpected AEs. This trial is registered at www.clinicaltrials.gov (NCT01578707).
Identifiants
pubmed: 31512258
doi: 10.1002/ajh.25638
pmc: PMC6899718
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
Piperidines
0
Protein Kinase Inhibitors
0
Pyrazoles
0
Pyrimidines
0
ibrutinib
1X70OSD4VX
Adenine
JAC85A2161
ofatumumab
M95KG522R0
Banques de données
ClinicalTrials.gov
['NCT01578707']
Types de publication
Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1353-1363Subventions
Organisme : NCI NIH HHS
ID : R35 CA197734
Pays : United States
Organisme : Janssen Pharmaceuticals
Pays : International
Organisme : Pharmacyclics LLC, an AbbVie Company
Pays : International
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.
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