Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: An integrated analysis.
B-cell neoplasms
clinical results in lymphomas
lymphoid leukaemias
signalling therapies
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
09
08
2018
accepted:
15
10
2018
pubmed:
7
12
2018
medline:
28
12
2019
entrez:
4
12
2018
Statut:
ppublish
Résumé
Ibrutinib, a Bruton tyrosine kinase inhibitor, is approved for treatment of various B-cell malignancies. In ibrutinib clinical studies, low-grade haemorrhage was common, whereas major haemorrhage (MH) was infrequent. We analysed the incidence of and risk factors for MH from 15 ibrutinib clinical studies (N = 1768), including 4 randomised controlled trials (RCTs). Rates of any-grade bleeding were similar for single-agent ibrutinib and ibrutinib combinations (39% and 40%). Low-grade bleeding was more common in ibrutinib-treated than comparator-treated patients (35% and 15%), and early low-grade bleeding was not associated with MH. The proportion of MH in RCTs was higher with ibrutinib than comparators (4.4% vs. 2.8%), but after adjusting for longer exposure with ibrutinib (median 13 months vs. 6 months), the incidence of MH was similar (3.2 vs. 3.1 per 1000 person-months). MH led to treatment discontinuation in 1% of all ibrutinib-treated patients. Use of anticoagulants and/or antiplatelets (AC/AP) during the study was common (~50% of patients) and had an increased exposure-adjusted relative risk for MH in both the total ibrutinib-treated population (1.9; 95% confidence interval, 1.2-3.0) and RCT comparator-treated patients (2.4; 95% confidence interval, 1.0-5.6), indicating that ibrutinib may not alter the effect of AC/AP on the risk of MH in B-cell malignancies.
Identifiants
pubmed: 30506764
doi: 10.1111/bjh.15690
pmc: PMC6587776
doi:
Substances chimiques
Piperidines
0
Pyrazoles
0
Pyrimidines
0
ibrutinib
1X70OSD4VX
Adenine
JAC85A2161
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
558-569Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Informations de copyright
© 2018 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
Références
Lancet Oncol. 2016 Feb;17(2):200-211
pubmed: 26655421
Blood Adv. 2017 May 09;1(12):772-778
pubmed: 29296721
Chest. 2010 Nov;138(5):1093-100
pubmed: 20299623
N Engl J Med. 2013 Jul 4;369(1):32-42
pubmed: 23782158
N Engl J Med. 2014 Jul 17;371(3):213-23
pubmed: 24881631
Clin Lymphoma Myeloma Leuk. 2017 Jan;17(1):31-37.e13
pubmed: 27780690
Blood. 2015 Aug 6;126(6):739-45
pubmed: 26059948
Clin Cancer Res. 2017 Mar 1;23(5):1149-1155
pubmed: 28073846
Blood. 2014 Dec 18;124(26):3991-5
pubmed: 25305202
Blood. 2018 Jan 25;131(4):379-386
pubmed: 29255067
J Thromb Haemost. 2005 Apr;3(4):692-4
pubmed: 15842354
Br J Haematol. 2017 Jul;178(2):286-291
pubmed: 28397242
Lancet. 2016 Feb 20;387(10020):770-8
pubmed: 26673811
Blood Adv. 2017 Sep 08;1(20):1739-1748
pubmed: 29296820
Leukemia. 2015 Apr;29(4):783-7
pubmed: 25138588
Blood. 2016 Jan 28;127(4):411-9
pubmed: 26542378
Blood. 2003 Nov 15;102(10):3592-9
pubmed: 12842985
N Engl J Med. 2015 Apr 9;372(15):1430-40
pubmed: 25853747
N Engl J Med. 2013 Aug 8;369(6):507-16
pubmed: 23782157
N Engl J Med. 2015 Dec 17;373(25):2425-37
pubmed: 26639149
Haematologica. 2017 Oct;102(10):1796-1805
pubmed: 28751558
J Thromb Haemost. 2017 May;15(5):835-847
pubmed: 28182323
N Engl J Med. 2016 Jan 28;374(4):323-32
pubmed: 26641137
Arterioscler Thromb Vasc Biol. 2015 Nov;35(11):2326-35
pubmed: 26359510
Haematologica. 2015 Dec;100(12):1571-8
pubmed: 26430171
Blood. 2015 Apr 16;125(16):2497-506
pubmed: 25700432
Thromb Res. 2016 Apr;140 Suppl 1:S196
pubmed: 27161742
Leukemia. 2017 May;31(5):1117-1122
pubmed: 27909342