IMBRUVICA ® (ibrutinib)
Table 5: Adverse Reactions Reported in ≥ 10% of Patients and
at Least 2% Greater in the IMBRUVICA Treated Arm
in Patients with CLL/SLL in RESONATE (continued)
IMBRUVICA
Ofatumumab
(N=195)
(N=191)
All Grades Grade 3 or 4 All Grades Grade 3 or 4
(%)
(%)
(%)
(%)
Body System
Adverse Reaction
Musculoskeletal
and connective
tissue disorders
Musculoskeletal
28
2
18
1
pain*
Arthralgia
17
1
7
0
Nervous system
disorders
Headache
14
1
6
0
Dizziness
11
0
5
0
Injury, poisoning
and procedural
complications
Contusion
11
0
3
0
Eye disorders
Vision blurred
10
0
3
0
Subjects with multiple events for a given ADR term are counted once only
for each ADR term.
The body system and individual ADR terms are sorted in descending frequency
order in the IMBRUVICA arm.
* Includes multiple ADR terms
Table 6: Treatment-Emergent Hematologic Laboratory Abnormalities
in Patients with CLL/SLL in RESONATE
IMBRUVICA
Ofatumumab
(N=195)
(N=191)
All Grades Grade 3 or 4 All Grades Grade 3 or 4
(%)
(%)
(%)
(%)
Neutrophils
51
23
57
26
Decreased
Platelets
52
5
45
10
Decreased
Hemoglobin
36
0
21
0
Decreased
RESONATE-2: Adverse reactions described below in Table 7 reflect
exposure to IMBRUVICA with a median duration of 17.4 months. The median
exposure to chlorambucil was 7.1 months in RESONATE-2.
Table 7: Adverse Reactions Reported in ≥ 10% of Patients and
at Least 2% Greater in the IMBRUVICA Treated Arm in Patients
with CLL/SLL in RESONATE-2
IMBRUVICA
Chlorambucil
(N=135)
(N=132)
Body System
All Grades Grade 3 or 4 All Grades Grade 3 or 4
Adverse Reaction
(%)
(%)
(%)
(%)
Gastrointestinal
disorders
Diarrhea
42
4
17
0
Stomatitis*
14
1
4
1
Musculoskeletal and
connective tissue
disorders
Musculoskeletal
36
4
20
0
pain*
Arthralgia
16
1
7
1
Muscle spasms
11
0
5
0
Eye disorders
Dry eye
17
0
5
0
Lacrimation
13
0
6
0
increased
Vision blurred
13
0
8
0
Visual acuity
11
0
2
0
reduced
IMBRUVICA ® (ibrutinib)
Table 7: Adverse Reactions Reported in ≥ 10% of Patients and
at Least 2% Greater in the IMBRUVICA Treated Arm in Patients
with CLL/SLL in RESONATE-2 (continued)
IMBRUVICA
Chlorambucil
(N=135)
(N=132)
All Grades Grade 3 or 4 All Grades Grade 3 or 4
Body System
(%)
(%)
(%)
(%)
Adverse Reaction
Skin and
subcutaneous tissue
disorders
Rash*
21
4
12
2
Bruising*
19
0
7
0
Infections and
infestations
Skin infection*
15
2
3
1
Pneumonia*
14
8
7
4
Urinary tract
10
1
8
1
infections
Respiratory, thoracic
and mediastinal
disorders
Cough
22
0
15
0
General disorders and
administration site
conditions
Peripheral edema
19
1
9
0
Pyrexia
17
0
14
2
Vascular disorders
Hypertension*
14
4
1
0
Nervous system
disorders
Headache
12
1
10
2
Subjects with multiple events for a given ADR term are counted once only
for each ADR term.
The body system and individual ADR terms are sorted in descending frequency
order in the IMBRUVICA arm.
* Includes multiple ADR terms
HELIOS: Adverse reactions described below in Table 8 reflect exposure
to IMBRUVICA + BR with a median duration of 14.7 months and exposure
to placebo + BR with a median of 12.8 months in HELIOS in patients with
previously treated CLL/SLL.
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
Ibrutinib + BR
Placebo + BR
(N=287)
(N=287)
Body System
All Grades Grade 3 or 4 All Grades Grade 3 or 4
Adverse Reaction
(%)
(%)
(%)
(%)
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
29
2
20
0
pain*
Muscle spasms
12
<1
5
0
General disorders
and administration
site conditions
Pyrexia
25
4
22
2