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IMBRUVICA ® (ibrutinib) capsules IMBRUVICA ® (ibrutinib) capsules
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 (continued)
Ibrutinib + BR
Placebo + BR
(N=287)
(N=287)
All Grades Grade 3 or 4 All Grades Grade 3 or 4
Body System
(%)
(%)
(%)
(%)
Adverse Reaction
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
The body system and individual ADR terms are sorted in descending frequency
order in the IMBRUVICA arm.
* Includes multiple ADR terms
<1 used for frequency above 0 and below 0.5% Table 9: Non-Hematologic Adverse Reactions in ≥ 10%
in Patients with WM in Study 1118 (N=63) (continued)
Grade 3
Body System
Adverse
All
or 4
Reaction
Grades
(%)
(%)
Respiratory, thoracic and Epistaxis
19
0
mediastinal disorders
Cough
13
0
Dizziness
14
0
Nervous system
disorders
Headache
13
0
Neoplasms benign,
Skin cancer*
11
0
malignant, and
unspecified (including
cysts and polyps)
The body system and individual ADR preferred terms are sorted in descending
frequency order.
* Includes multiple ADR terms.
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 reflect exposure to IMBRUVICA with a median duration
of 11.7 months in Study 1118.
Table 9: Non-Hematologic Adverse Reactions in ≥ 10%
in Patients with WM in Study 1118 (N=63)
Grade 3
Body System
Adverse
All
or 4
Reaction
Grades
(%)
(%)
Gastrointestinal
Diarrhea
37
0
disorders
Nausea
21
0
Stomatitis*
16
0
Gastroesophageal
reflux disease
13
0
Skin and subcutaneous
Rash*
22
0
tissue disorders
Bruising*
16
0
Pruritus
11
0
General disorders and
Fatigue
21
0
administrative site
conditions
Musculoskeletal and
Muscle spasms
21
0
connective tissue
Arthropathy
13
0
disorders
Infections and
Upper
infestations
respiratory
tract infection
19
0
Sinusitis
19
0
Pneumonia*
14
6
Skin infection*
14
2
Table 10: Treatment-Emergent Hematologic Laboratory Abnormalities
in Patients with WM in Study 1118 (N=63)
Percent of Patients (N=63)
All Grades (%)
Grade 3 or 4 (%)
Platelets Decreased
43
13
Neutrophils Decreased
44
19
Hemoglobin Decreased
13
8
Study 1121: Adverse reactions and laboratory abnormalities described below
in Tables 11 and 12 reflect exposure to IMBRUVICA with a median duration
of 11.6 months in Study 1121.
Table 11: Non-Hematologic Adverse Reactions in ≥ 10% in Patients
with MZL in Study 1121 (N=63)
Body System
Adverse Reaction
All
Grade 3
Grades
or 4
(%)
(%)
Gastrointestinal
Diarrhea
43
5
disorders
Nausea
25
0
Dyspepsia
19
0
Stomatitis*
17
2
Abdominal pain
16
2
Constipation
14
0
Abdominal pain Upper
13
0
Vomiting
11
2
General disorders
Fatigue
44
6
and administrative
Peripheral edema
24
2
site conditions
Pyrexia
17
2
Skin and
Bruising *
41
0
subcutaneous tissue Rash*
29
5
disorders
Pruritus
14
0
Musculoskeletal and Musculoskeletal
connective tissue
pain*
40
3
disorders
Arthralgia
24
2
Muscle spasms
19
3
Infections and
Upper respiratory
infestations
tract infection
21
0
Sinusitis*
19
0
Bronchitis
11
0
Pneumonia*
11
10
Metabolism and
Decreased appetite
16
2
nutrition disorders
Hyperuricemia
16
0
Hypoalbuminemia
14
0
Hypokalemia
13
0
Vascular Disorders
Hemorrhage*
30
0
Hypertension*
14
5
Respiratory, thoracic Cough
22
2
and mediastinal
Dyspnea
21
2
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.