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)
Grade 3
All
Grade 3
All
Grades or Higher Grades or Higher
Body System
(%)
(%)
(%)
(%)
Adverse Reaction
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%
† Includes 2 events of hemorrhage with fatal outcome in the IMBRUVICA arm
and 1 event of neutropenia with a fatal outcome in the placebo + BR arm.
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.
iLLUMINATE: Adverse reactions described below in Table 9 reflect exposure
to IMBRUVICA + obinutuzumab with a median duration of 29.3 months and
exposure to chlorambucil + obinutuzumab with a median of 5.1 months in
iLLUMINATE in patients with previously untreated CLL/SLL. Table 9: Adverse Reactions Reported in at Least 10% of Patients in the
IMBRUVICA Arm in Patients with CLL/SLL in iLLUMINATE (continued)
Chlorambucil +
IMBRUVICA +
Obinutuzumab
Obinutuzumab
(N=115)
(N=113)
Grade 3
All
Grade 3
All
Grades or Higher Grades or Higher
Body System
(%)
(%)
(%)
(%)
Adverse Reaction §
Metabolism and Nutrition
Disorders
Hyperuricemia
13
1
0
0
Cardiac Disorders
Atrial Fibrillation
12
5
0
0
General Disorders and
Administration Site
Conditions
Pyrexia
19
2
26
1
Fatigue
18
0
17
2
Peripheral edema
12
0
7
0
Psychiatric disorders
Insomnia
12
0
4
0
§ The data are not an adequate basis for comparison of ADR rates between
treatment arms.
The body system and individual ADR terms are sorted in descending frequency
order in the IMBRUVICA arm.
* Includes multiple ADR terms
† Includes one event with a fatal outcome.
Table 9: Adverse Reactions Reported in at Least 10% of Patients in the
IMBRUVICA Arm in Patients with CLL/SLL in iLLUMINATE
Chlorambucil +
IMBRUVICA +
Obinutuzumab
Obinutuzumab
(N=115)
(N=113)
Grade 3
All
Grade 3
All
Grades or Higher Grades or Higher
Body System
§
(%)
(%)
(%)
(%)
Adverse Reaction
Blood and lymphatic system
disorders
Neutropenia*
48
39
64
48
Thrombocytopenia*
36
19
28
11
Anemia
17
4
25
8
Skin and subcutaneous tissue
disorders
Rash*
36
3
11
0
Bruising*
32
3
3
0
Gastrointestinal Disorders
Diarrhea
34
3
10
0
Constipation
16
0
12
1
Nausea
12
0
30
0
Musculoskeletal and
Connective Tissue Disorders
Musculoskeletal Pain*
33
1
23
3
Arthralgia
22
1
10
0
Muscle spasms
13
0
6
0
Respiratory, Thoracic and
Mediastinal Disorders
Cough
27
1
12
0
Injury, Poisoning and
Procedural Complications
Infusion related reaction
25
2
58
8
Vascular disorders
Hemorrhage*
25
1
9
0
Hypertension*
17
4
4
3
Infections and Infestations
Pneumonia*
16
9
9
4 †
Upper Respiratory Tract
14
1
6
0
Infection
Skin infection*
13
1
3
0
Urinary tract infection
12
3
7
1
Nasopharyngitis
12
0
3
0
Conjunctivitis
11
0
2
0
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 10 and 11 reflect
exposure to IMBRUVICA with a median duration of 11.7 months in
Study 1118 and 33 months in the INNOVATE Monotherapy Arm.
Table 10: Non-Hematologic Adverse Reactions in ≥ 10% in Patients with
WM in Study 1118 and the INNOVATE Monotherapy Arm (N=94)
Grade 3
All
Grades or Higher
(%)
(%)
Body System
Adverse Reaction
2
38
Gastrointestinal
Diarrhea
0
21
disorders
Nausea
0
15
Stomatitis*
1
12
Constipation
Gastroesophageal
0
12
reflux disease
Skin and subcutaneous Bruising*
28
1
tissue disorders
Rash*
21
1
Vascular disorders
Hemorrhage*
28
0
Hypertension*
14
4
Fatigue
18
2
General disorders and
Pyrexia
12
2
administrative site
conditions
Musculoskeletal pain*
21
0
Musculoskeletal and
Muscle spasms
19
0
connective tissue
disorders