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

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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.

authors

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

publication date

  • February 2019