IMBRUVICA ® (ibrutinib)
IMBRUVICA ® (ibrutinib)
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
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%
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 three single-arm open-
label clinical trials (Study 1118, Study 1121, and INNOVATE monotherapy
arm) and one randomized controlled trial (INNOVATE) in patients with WM
or MZL, including a total n=307 patients overall and n=232 patients exposed
to IMBRUVICA. Study 1118 included 63 patients with previously treated WM
who received single agent IMBRUVICA. Study 1121 included 63 patients
with previously treated MZL who received single agent IMBRUVICA.
INNOVATE included 150 patients with treatment naïve or previously treated
WM who received IMBRUVICA or placebo in combination with rituximab.
The INNOVATE monotherapy arm included 31 patients with previously
treated WM who failed prior rituximab-containing therapy and received
IMBRUVICA.
The most commonly occurring adverse reactions in Studies 1118, 1121, and
INNOVATE (≥ 20%) were thrombocytopenia, diarrhea, bruising, neutropenia,
musculoskeletal pain, hemorrhage, anemia, rash, fatigue, and nausea.
Seven percent of patients receiving IMBRUVICA across Studies 1118, 1121,
and INNOVATE discontinued treatment due to adverse reactions. The most
common adverse reactions leading to discontinuation were atrial fibrillation,
interstitial lung disease, diarrhea and rash. Adverse reactions leading to dose
reduction occurred in 13% of patients.
Study 1118 and INNOVATE Monotherapy Arm: 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 and
33 months in the INNOVATE Monotherapy Arm.
Table 9: Non-Hematologic Adverse Reactions in ≥ 10% in Patients with
WM in Study 1118 and the INNOVATE Monotherapy Arm (N=94)
All Grades Grade 3 or 4
Body System
Adverse Reaction
(%)
(%)
2
38
Gastrointestinal
Diarrhea
0
21
disorders
Nausea
0
15
Stomatitis*
1
12
Constipation
0
12
Gastroesophageal
reflux disease
Skin and subcutaneous Bruising*
28
1
tissue disorders
Rash*
21
1
Vascular disorders
Hemorrhage*
28
0
Hypertension*
14
4
18
2
General disorders and Fatigue
Pyrexia
12
2
administrative site
conditions
Musculoskeletal pain*
21
0
Musculoskeletal and
Muscle spasms
19
0
connective tissue
disorders
Table 9: Non-Hematologic Adverse Reactions in ≥ 10% in Patients
with WM in Study 1118 and the INNOVATE Monotherapy Arm (N=94)
(continued)
Body System
Infections and
infestations
Nervous system
disorders
Respiratory, thoracic
and mediastinal
disorders
Adverse Reaction
Upper respiratory
tract infection
Skin infection*
Sinusitis*
Pneumonia*
Headache
Dizziness
Cough
All
Grades
(%)
19 Grade 3
or 4
(%)
0
18
16
13
14
13
13 3
0
5
0
0
0
The body system and individual ADR preferred terms are sorted in descending
frequency order.
* Includes multiple ADR terms.
Table 10: Treatment-Emergent Hematologic Laboratory Abnormalities
in Patients with WM in Study 1118 and the INNOVATE
Monotherapy Arm (N=94)
Platelets Decreased
Neutrophils Decreased
Hemoglobin Decreased
Percent of Patients (N=94)
All Grades (%)
Grade 3 or 4 (%)
38
11
43
16
21
6
INNOVATE: Adverse reactions described below in Table 11 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 11: 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 Grades Grade 3 or 4 All Grades Grade 3
(%)
(%)
(%)
or 4
(%)
Skin and
subcutaneous tissue
disorders
Bruising*
37
1
5
0
Rash*
24
1
11
0
Musculoskeletal and
connective tissue
disorders
Musculoskeletal
35
4
21
3
pain*
Arthralgia
24
3
11
1
Muscle spasms
17
0
12
1
Vascular disorders
Hemorrhage*
32
3
17
3
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