Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: An integrated analysis

Jennifer R. Brown; Javid Moslehi; Michael S. Ewer; Susan M. O'Brien; Paolo Ghia; Florence Cymbalista; Tait D. Shanafelt; Graeme Fraser; Simon Rule; Steven E. Coutre; Marie Sarah Dilhuydy; Paula Cramer; Ulrich Jaeger; Martin Dreyling; John C. Byrd; Steven Treon; Emily Y. Liu; Stephen Chang; Amulya Bista; Rama Vempati; Lisa Boornazian; Rudolph Valentino; Vijay Reddy; Michelle Mahler; Huiying Yang; Thorsten Graef; Jan A. Burger

doi:10.1111/bjh.15690

Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: An integrated analysis

Jennifer R. Brown, Javid Moslehi, Michael S. Ewer, Susan M. O'Brien, Paolo Ghia, Florence Cymbalista, Tait D. Shanafelt, Graeme Fraser, Simon Rule, Steven E. Coutre, Marie Sarah Dilhuydy, Paula Cramer, Ulrich Jaeger, Martin Dreyling, John C. Byrd, Steven Treon, Emily Y. Liu, Stephen Chang, Amulya Bista, Rama VempatiLisa Boornazian, Rudolph Valentino, Vijay Reddy, Michelle Mahler, Huiying Yang, Thorsten Graef, Jan A. Burger

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	558-569
Number of pages	12
Journal	British Journal of Haematology
Volume	184
Issue number	4
DOIs	https://doi.org/10.1111/bjh.15690
State	Published - Feb 2019

Keywords

B-cell neoplasms
clinical results in lymphomas
lymphoid leukaemias
signalling therapies

ASJC Scopus subject areas

Hematology

Access to Document

10.1111/bjh.15690

Cite this

Brown, J. R., Moslehi, J., Ewer, M. S., O'Brien, S. M., Ghia, P., Cymbalista, F., Shanafelt, T. D., Fraser, G., Rule, S., Coutre, S. E., Dilhuydy, M. S., Cramer, P., Jaeger, U., Dreyling, M., Byrd, J. C., Treon, S., Liu, E. Y., Chang, S., Bista, A., ... Burger, J. A. (2019). Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: An integrated analysis. British Journal of Haematology, 184(4), 558-569. https://doi.org/10.1111/bjh.15690

Brown, JR, Moslehi, J, Ewer, MS, O'Brien, SM, Ghia, P, Cymbalista, F, Shanafelt, TD, Fraser, G, Rule, S, Coutre, SE, Dilhuydy, MS, Cramer, P, Jaeger, U, Dreyling, M, Byrd, JC, Treon, S, Liu, EY, Chang, S, Bista, A, Vempati, R, Boornazian, L, Valentino, R, Reddy, V, Mahler, M, Yang, H, Graef, T & Burger, JA 2019, 'Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: An integrated analysis', British Journal of Haematology, vol. 184, no. 4, pp. 558-569. https://doi.org/10.1111/bjh.15690

@article{2f39920279db4eaeb8ac86a840807ee4,

title = "Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: An integrated analysis",

abstract = "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.",

keywords = "B-cell neoplasms, clinical results in lymphomas, lymphoid leukaemias, signalling therapies",

author = "Brown, {Jennifer R.} and Javid Moslehi and Ewer, {Michael S.} and O'Brien, {Susan M.} and Paolo Ghia and Florence Cymbalista and Shanafelt, {Tait D.} and Graeme Fraser and Simon Rule and Coutre, {Steven E.} and Dilhuydy, {Marie Sarah} and Paula Cramer and Ulrich Jaeger and Martin Dreyling and Byrd, {John C.} and Steven Treon and Liu, {Emily Y.} and Stephen Chang and Amulya Bista and Rama Vempati and Lisa Boornazian and Rudolph Valentino and Vijay Reddy and Michelle Mahler and Huiying Yang and Thorsten Graef and Burger, {Jan A.}",

note = "Publisher Copyright: {\textcopyright} 2018 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd",

year = "2019",

month = feb,

doi = "10.1111/bjh.15690",

language = "English (US)",

volume = "184",

pages = "558--569",

journal = "British Journal of Haematology",

issn = "0007-1048",

publisher = "Wiley-Blackwell",

number = "4",

}

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

Y1 - 2019/2

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

UR - http://www.scopus.com/inward/record.url?scp=85057732951&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85057732951&partnerID=8YFLogxK

U2 - 10.1111/bjh.15690

DO - 10.1111/bjh.15690

M3 - Article

C2 - 30506764

AN - SCOPUS:85057732951

SN - 0007-1048

VL - 184

SP - 558

EP - 569

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 4

ER -

Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: An integrated analysis

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this