TY - JOUR
T1 - Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib
T2 - An integrated analysis
AU - Brown, Jennifer R.
AU - Moslehi, Javid
AU - Ewer, Michael S.
AU - O'Brien, Susan M.
AU - Ghia, Paolo
AU - Cymbalista, Florence
AU - Shanafelt, Tait D.
AU - Fraser, Graeme
AU - Rule, Simon
AU - Coutre, Steven E.
AU - Dilhuydy, Marie Sarah
AU - Cramer, Paula
AU - Jaeger, Ulrich
AU - Dreyling, Martin
AU - Byrd, John C.
AU - Treon, Steven
AU - Liu, Emily Y.
AU - Chang, Stephen
AU - Bista, Amulya
AU - Vempati, Rama
AU - Boornazian, Lisa
AU - Valentino, Rudolph
AU - Reddy, Vijay
AU - Mahler, Michelle
AU - Yang, Huiying
AU - Graef, Thorsten
AU - Burger, Jan A.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
KW - B-cell neoplasms
KW - clinical results in lymphomas
KW - lymphoid leukaemias
KW - signalling therapies
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U2 - 10.1111/bjh.15690
DO - 10.1111/bjh.15690
M3 - Article
C2 - 30506764
AN - SCOPUS:85057732951
VL - 184
SP - 558
EP - 569
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 4
ER -