Table 4 : Treatment-Emergent * Hematologic Laboratory Abnormalities | ||||
in Patients with CLL / SLL ( N = 51 ) in Study 1102 | ||||
Percent of Patients ( N = 51 ) | ||||
All Grades (%) |
Grade 3 or 4 (%) |
|||
Platelets Decreased |
69 |
12 |
||
Neutrophils Decreased |
53 |
26 |
||
Hemoglobin Decreased |
43 |
0 |
||
* Based on laboratory measurements per IWCLL criteria and adverse reactions . | ||||
RESONATE : Adverse reactions and laboratory abnormalities described below in Tables 5 and 6 | ||||
reflect exposure to IMBRUVICA with a median duration of 8.6 months and exposure to ofatumumab | ||||
with a median of 5.3 months in RESONATE in patients with previously treated CLL / SLL . | ||||
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 | ||||
IMBRUVICA ( N = 195 ) |
Ofatumumab ( N = 191 ) |
|||
Body System Adverse Reaction |
All Grades (%) |
Grade 3 or 4 (%) |
All Grades (%) |
Grade 3 or 4 (%) |
Gastrointestinal disorders Diarrhea |
48 |
4 |
18 |
2 |
Nausea |
26 |
2 |
18 |
0 |
Stomatitis * |
17 |
1 |
6 |
1 |
Constipation |
15 |
0 |
9 |
0 |
Vomiting |
14 |
0 |
6 |
1 |
General disorders and administration site conditions
Pyrexia
|
24 |
2 |
15 |
1 |
Infections and infestations Upper respiratory tract infection |
16 |
1 |
11 |
2 |
Pneumonia * |
15 |
10 |
13 |
9 |
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 |
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 |
Table 6 : Treatment-Emergent Hematologic Laboratory Abnormalities | ||||
in Patients with CLL / SLL in RESONATE | ||||
IMBRUVICA ( N = 195 ) |
Ofatumumab ( N = 191 ) |
|||
All Grades (%) |
Grade 3 or 4 (%) |
All Grades (%) |
Grade 3 or 4 (%) |
|
Neutrophils Decreased |
51 |
23 |
57 |
26 |
Platelets Decreased |
52 |
5 |
45 |
10 |
Hemoglobin Decreased |
36 |
0 |
21 |
0 |
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 ( N = 135 ) |
Chlorambucil ( N = 132 ) |
|||
Body System Adverse Reaction |
All Grades (%) |
Grade 3 or 4 (%) |
All Grades (%) |
Grade 3 or 4 (%) |
Gastrointestinal disorders Diarrhea |
42 |
4 |
17 |
0 |
Stomatitis * |
14 |
1 |
4 |
1 |
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 Skin infection * |
15 |
2 |
3 |
1 |
Pneumonia * |
14 |
8 |
7 |
4 |
Urinary tract infections |
10 |
1 |
8 |
1 |
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 ( N = 135 ) |
Chlorambucil ( N = 132 ) |
|||
Body System Adverse Reaction |
All Grades (%) |
Grade 3 or 4 (%) |
All Grades (%) |
Grade 3 or 4 (%) |
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 . |
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 pain *
|
29 |
2 |
20 |
0 |
Muscle spasms |
12 |
< 1 |
5 |
0 |
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 % | ||||
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 ) | ||||
Body System |
Adverse Reaction |
All Grades (%) |
Grade 3 or 4 (%) |