Table 1.

Incidence of bleeding events with ibrutinib.^*

Trial	Phase	Comparison	Median follow up	Any bleeding (%)	Grade 1–2 hemorrhage (%)	Major hemorrhage Grade III-IV (%)	Fatal hemorrhage (%)	Major hemorrhage on concomitant AC, antiplatelet, or Vitamin E (%)	Median time to major hemorrhage	Thrombocytopenia Grade 1–2 (%)	Thrombocytopenia Grade 3–4 (%)	Held for procedures /surgery	Excluded warfarin?	ASA during study (%)	Clopidogrel during study (%)	AC during study (%)
Chanan- Kahn, Lancet 2016	Phase III	Ibrutinib R- Benda (n=287) Vs. R-Benda (N=287), CLL	17 mo	31% vs 15%	28% vs 9%	4% vs. 2%	0.6% vs 0	54% (6/11) vs 60% (3/5)	4.2 mo vs 2.3 mo	16% vs 9%	15 vs 15	Not reported	YES
Burger, NEJM 2015	Phase III	Ibrutinb (N=136 )Vs. Chlorambacil (N=133), CLL	18.4 mo	Not Reported	Not Reported	4% vs. 2%	0 vs 0	50% (3/6) vs not reported	Not Reported	Not Reported	2% vs 6%	YES (14 days)	YES
Byrd, NEJM 2014	Phase III	Ibrutinib (N=195) Vs. Ofatumumab (N= 196), CLL	9.4 mo	44% vs 12%	27% vs 10%	1% vs 2%	0 vs 0	Not Reported	Not Reported	11% vs 8%	6% vs 4%	YES	YES
Dreyling, Lancet 2016	Phase III	Ibrutinib (N=139) Vs. temsirolimus (N= 141), MCL	20 mo	Not Reported	Not Reported	10%vs 6%	0 vs 0	Not Reported	Not Reported	9% vs 14%	9% vs 42%	Not reported	YES
Byrd, Blood 2015	Phase II	Ibrutinib (N=132) CLL	36 mo	61%	53%	8%	0.7%(1)	Not Reported	Not Reported	Not Reported	8%	Later in protocol. 3 days for minor, 7 days for major	Later in protocol	33%	2%	22%
Wang, Blood 2015	Phase II	Ibrutinib (N= 111 ) MCL	26.7 mo	50%	44%	6%	0	85% (6/7) (includes NSAID) Bleeding events were higher in those on AC/anti plt: (69% any grade, 8% grade 3–4) vs those not receiving these treatments (28% any grade, 4% grade 3–4).	Not Reported (41% were in the first 6mo)	9%	13%	Not reported	Later in protocol	26%	6%	24% (14% LMWH, 10% Warfari n)

^*Phase III and selected phase II trials with over 100 patients, reporting bleeding events.