IMBRUVICA ® (ibrutinib) IMBRUVICA ® (ibrutinib)
Table 5: Adverse Reactions Reported in ≥ 10% of Patients in the IMBRUVICA
Treated Arm in Patients with CLL/SLL in RESONATE (continued)
IMBRUVICA
Ofatumumab
(N=195)
(N=191)
Grade 3
All
Grade 3
All
Grades or Higher Grades or Higher
Body System
(%)
(%)
(%)
(%)
Adverse Reaction
Infections and infestations
Upper respiratory tract infection
16
1
11
2 †
Pneumonia*
15
12 †
13
10 †
Sinusitis*
11
1
6
0
Urinary tract infection
10
4
5
1
Skin and subcutaneous tissue
disorders
Rash*
24
3
13
0
Petechiae
14
0
1
0
Bruising*
12
0
1
0
Musculoskeletal and
connective tissue disorders
Musculoskeletal pain*
28
2
18
1
Arthralgia
17
1
7
0
Muscle spasms
13
0
8
0
Respiratory, thoracic and
mediastinal disorders
Cough
19
0
23
1
Dyspnea
12
2
10
1
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
The body system and individual ADR terms are sorted in descending frequency
order in the IMBRUVICA arm.
* Includes multiple ADR terms
† Includes 3 events of pneumonia with fatal outcome in each arm, and 1 event
of pyrexia and upper respiratory tract infection with a fatal outcome in the
ofatumumab arm. Table 7: Adverse Reactions Reported in ≥ 10% of Patients in the IMBRUVICA
Treated Arm in Patients with CLL/SLL in RESONATE-2 (continued)
IMBRUVICA
Chlorambucil
(N=135)
(N=132)
Grade 3
All
Grade 3
All
Grades or Higher Grades or Higher
Body System
(%)
(%)
(%)
(%)
Adverse Reaction
Musculoskeletal and
connective tissue disorders
Musculoskeletal pain*
36
4
20
0
Arthralgia
16
1
7
1
Muscle spasms
11
0
5
0
Eye disorders
Dry eye
17
0
5
0
Lacrimation increased
13
0
6
0
Vision blurred
13
0
8
0
Visual acuity reduced
11
0
2
0
Skin and subcutaneous
tissue disorders
Rash*
21
4
12
2
Bruising*
19
0
7
0
Infections and infestations
Upper respiratory tract
17
2
17
2
infection
Skin infection*
15
2
3
1
Pneumonia*
14
8
7
4
Urinary tract infections
10
1
8
1
Respiratory, thoracic and
mediastinal disorders
Cough
22
0
15
0
Dyspnea
10
1
10
0
General disorders and
administration site
conditions
Fatigue
30
1
38
5
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
Dizziness
11
0
12
1
Investigations
Weight decreased
10
0
12
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)
Grade
All
Grade
All
3 or 4
Grades
3 or 4
Grades
(%)
(%)
(%)
(%)
Neutrophils Decreased
51
23
57
26
Platelets Decreased
52
5
45
10
Hemoglobin Decreased
36
0
21
0
Treatment-emergent Grade 4 thrombocytopenia (2% in the IMBRUVICA arm
vs 3% in the ofatumumab arm) and neutropenia (8% in the IMBRUVICA arm
vs 8% in the ofatumumab arm) occurred in patients.
RESONATE-2: Adverse reactions and laboratory abnormalities described
below in Tables 7 and 8 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 in the IMBRUVICA
Treated Arm in Patients with CLL/SLL in RESONATE-2
IMBRUVICA
Chlorambucil
(N=135)
(N=132)
Grade 3
All
Grade 3
All
Grades or Higher Grades or Higher
Body System
(%)
(%)
(%)
(%)
Adverse Reaction
Gastrointestinal disorders
Diarrhea
42
4
17
0
Nausea
22
1
39
1
Constipation
16
1
16
0
Stomatitis*
14
1
4
1
Vomiting
13
0
20
1
Abdominal pain
13
3
11
1
Dyspepsia
11
0
2
0
Table 8: Treatment-Emergent Hematologic Laboratory Abnormalities
in Patients with CLL/SLL in RESONATE-2
IMBRUVICA
Chlorambucil
(N=135)
(N=132)
All Grades Grade 3 or 4 All Grades Grade 3 or 4
(%)
(%)
(%)
(%)
Neutrophils Decreased
55
28
67
31
Platelets Decreased
47
7
58
14
Hemoglobin Decreased
36
0
39
2
Treatment-emergent Grade 4 thrombocytopenia (1% in the IMBRUVICA arm
vs 3% in the chlorambucil arm) and neutropenia (11% in the IMBRUVICA arm
vs 12% in the chlorambucil arm) occurred in patients.
HELIOS: Adverse reactions described below in Table 9 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.