IMBRUVICA ® (ibrutinib) IMBRUVICA ® (ibrutinib)
Table 10: Non-Hematologic Adverse Reactions in ≥ 10% in Patients
with WM in Study 1118 and the INNOVATE Monotherapy Arm (N=94)
(continued)
Grade 3
All
Grades or Higher
(%)
(%)
Body System
Adverse Reaction
Infections and
Upper respiratory tract
19
0
infestations
infection
Skin infection*
18
3
Sinusitis*
16
0
Pneumonia*
13
5
Nervous system
Headache
14
0
disorders
Dizziness
13
0
Respiratory, thoracic
Cough
13
0
and mediastinal
disorders
The body system and individual ADR preferred terms are sorted in descending
frequency order.
* Includes multiple ADR terms.
Table 11: Treatment-Emergent Hematologic Laboratory Abnormalities
in Patients with WM in Study 1118 and the INNOVATE
Monotherapy Arm (N=94)
Percent of Patients (N=94)
All Grades (%)
Grade 3 or 4 (%)
Platelets Decreased
38
11
Neutrophils Decreased
43
16
Hemoglobin Decreased
21
6
Treatment-emergent Grade 4 thrombocytopenia (4%) and neutropenia (7%)
occurred in patients.
INNOVATE: Adverse reactions described below in Table 12 reflect exposure to
IMBRUVICA + R with a median duration of 25.8 months and exposure to placebo
+ R with a median duration of 15.5 months in patients with treatment naïve or
previously treated WM in INNOVATE.
Table 12: Adverse Reactions Reported in at Least 10% of Patients and at
Least 2% Greater in the IMBRUVICA Arm in Patients with WM in INNOVATE
Body System
IMBRUVICA + R
Placebo + R
Adverse Reaction
(N=75)
(N=75)
All
Grade 3
All
Grade 3
Grades or Higher Grades or Higher
(%)
(%)
(%)
(%)
Skin and subcutaneous
tissue disorders
Bruising*
37
1
5
0
Rash*
24
1
11
0
Musculoskeletal and
connective tissue disorders
Musculoskeletal pain*
35
4
21
3
Arthralgia
24
3
11
1
Muscle spasms
17
0
12
1
Vascular disorders
Hemorrhage*
32
3
17
4 †
Hypertension*
20
13
5
4
Gastrointestinal disorders
Diarrhea
28
0
15
1
Nausea
21
0
12
0
Dyspepsia
16
0
1
0
Constipation
13
1
11
1
Infections and infestations
Pneumonia*
19
13
5
3
Skin infection*
17
3
3
0
Urinary tract infection
13
0
0
0
Bronchitis
12
3
7
0
Influenza
12
0
7
1
Viral upper respiratory
11
0
7
0
tract infection
General disorders and
administration site
conditions
Peripheral edema
17
0
12
1
Respiratory, thoracic, and
mediastinal disorders
Cough
17
0
11
0 Table 12: Adverse Reactions Reported in at Least 10% of Patients and at
Least 2% Greater in the IMBRUVICA Arm in Patients with WM in INNOVATE
(continued)
IMBRUVICA + R
Placebo + R
Body System
(N=75)
(N=75)
Adverse Reaction
All
Grade 3
All
Grade 3
Grades or Higher Grades or Higher
(%)
(%)
(%)
(%)
Blood and Lymphatic System
Disorders
Neutropenia*
16
12
11
4
Cardiac Disorders
Atrial fibrillation
15
12
3
1
Nervous system disorders
Dizziness
11
0
7
0
Psychiatric disorders
Insomnia
11
0
4
0
Metabolism and nutrition
disorders
Hypokalemia
11
0
1
1
The body system and individual ADR preferred terms are sorted in descending
frequency order.
* Includes multiple ADR terms.
† Includes one event with a fatal outcome.
Grade 3 or 4 infusion related reactions were observed in 1% of patients treated
with IMBRUVICA + R.
Study 1121: Adverse reactions and laboratory abnormalities described below
in Tables 13 and 14 reflect exposure to IMBRUVICA with a median duration
of 11.6 months in Study 1121.
Table 13: Non-Hematologic Adverse Reactions in ≥ 10% in Patients
with MZL in Study 1121 (N=63)
Grade 3
All
Grades or Higher
(%)
(%)
Body System
Adverse Reaction
5
43
Gastrointestinal
Diarrhea
0
25
disorders
Nausea
0
19
Dyspepsia
2
17
Stomatitis*
2
16
Abdominal pain
0
14
Constipation
0
13
Abdominal pain upper
2
11
Vomiting
6
44
Fatigue
General disorders and
2
24
Peripheral edema
administrative site
2
17
Pyrexia
conditions
0
41
Skin and subcutaneous Bruising*
5
29
tissue disorders
Rash*
0
14
Pruritus
3
40
Musculoskeletal pain*
Musculoskeletal and
2
24
Arthralgia
connective tissue
3
19
Muscle spasms
disorders
Infections and
Upper respiratory tract
0
21
infestations
infection
0
19
Sinusitis*
0
11
Bronchitis
10
11
Pneumonia*
2
16
Metabolism and
Decreased appetite
0
16
nutrition disorders
Hyperuricemia
0
14
Hypoalbuminemia
0
13
Hypokalemia
Vascular disorders
Hemorrhage*
30
2 †
Hypertension*
14
5
Cough
22
2
Respiratory, thoracic
Dyspnea
21
2
and mediastinal
disorders
Nervous system
Dizziness
19
0
disorders
Headache
13
0
Psychiatric disorders
Anxiety
16
2
The body system and individual ADR preferred terms are sorted in descending
frequency order.
* Includes multiple ADR terms.
† Includes one event with a fatal outcome.