Table 8: Adverse Reactions Reported in at Least 10% of Patients and at Least 2% Greater in the IMBRUVICA Arm in Patients with CLL/SLL in HELIOS
Body System
Adverse Reaction Ibrutinib + BR
(N=287) Placebo + BR
(N=287)
All Grades
(%) Grade 3 or 4
(%) All Grades
(%) Grade 3 or 4
(%)
The body system and individual ADR terms are sorted in descending frequency order in the IMBRUVICA arm.
<1 used for frequency above 0 and below 0.5%
* Includes multiple ADR terms
Blood and lymphatic system disorders    
  Neutropenia* 66 61 60 55
  Thrombocytopenia* 34 16 26 16
Skin and subcutaneous tissue disorders    
  Rash * 32 4 25 1
  Bruising * 20 <1 8 <1
Gastrointestinal disorders    
  Diarrhea 36 2 23 1
  Abdominal pain 12 1 8 <1
Musculoskeletal and connective tissue disorders    
  Musculoskeletal pain * 29 2 20 0
  Muscle spasms 12 <1 5 0
General disorders and administration site conditions    
  Pyrexia 25 4 22 2
Vascular disorders    
  Hemorrhage* 19 2 9 1
  Hypertension * 11 5 5 2
Infections and infestations    
  Bronchitis 13 2 10 3
  Skin infection* 10 3 6 2
Metabolism and nutrition disorders    
  Hyperuricemia 10 2 6 0
Atrial fibrillation of any grade occurred in 7% of patients treated with IMBRUVICA + BR and 2% of patients treated with placebo + BR. The frequency of Grade 3 and 4 atrial fibrillation was 3% in patients treated with IMBRUVICA + BR and 1% in patients treated with placebo +BR.
Waldenström's Macroglobulinemia and Marginal Zone Lymphoma
The data described below reflect exposure to IMBRUVICA in open-label clinical trials that included 63 patients with previously treated WM (Study 1118) and 63 patients with previously treated MZL (Study 1121).
The most commonly occurring adverse reactions in Studies 1118 and 1121 (≥ 20%) were thrombocytopenia, diarrhea, neutropenia, fatigue, bruising, hemorrhage, anemia, rash, musculoskeletal pain, and nausea.
Nine percent of patients receiving IMBRUVICA across Studies 1118 and 1121 discontinued treatment due to adverse reactions. The most common adverse reactions leading to discontinuation were interstitial lung disease, diarrhea and rash. Adverse reactions leading to dose reduction occurred in 10% of patients.
Study 1118
Adverse reactions and laboratory abnormalities described below in TABLES 9 and 10 reflec