ASH Clinical News Advances in Hematology Research & Patient Care: Hi | Page 7
IMBRUVICA® (ibrutinib) capsules
IMBRUVICA® (ibrutinib) capsules
Patients with MCL who develop lymphocytosis greater than 400,000/mcL
have developed intracranial hemorrhage, lethargy, gait instability, and
headache. However, some of these cases were in the setting of disease
progression.
Forty percent of patients had elevated uric acid levels on study including
13% with values above 10 mg/dL. Adverse reaction of hyperuricemia was
reported for 15% of patients.
Chronic Lymphocytic Leukemia: The data described below reflect exposure
to IMBRUVICA in an open label clinical trial (Study 1) that included
48 patients with previously treated CLL and a randomized clinical trial
(Study 2) that included 391 randomized patients with previously treated
CLL or SLL.
The most commonly occurring adverse reactions in Study 1 and Study 2
(≥ 20%) were thrombocytopenia, neutropenia, diarrhea, anemia, fatigue,
musculoskeletal pain, upper respiratory tract infection, rash, nausea, and
pyrexia.
Approximately five percent of patients receiving IMBRUVICA in Study 1
and Study 2 discontinued treatment due to adverse events. These included
infections, subdural hematomas and diarrhea. Adverse events leading to
dose reduction occurred in approximately 6% of patients.
Study 1: Adverse reactions and laboratory abnormalities from the CLL trial
(N=48) using single agent IMBRUVICA 420 mg daily occurring at a rate of
≥ 10% are presented in Tables 3 and 4.
Table 3: Non-Hematologic Adverse Reactions in ≥ 10% of Patients
with CLL (N=48) in Study 1
System Organ Class
Gastrointestinal
disorders
Infections and
infestations
General disorders
and administrative
site conditions
Skin and
subcutaneous
tissue disorders
Respiratory, thoracic
and mediastinal
disorders
Musculoskeletal and
connective tissue
disorders
Nervous system
disorders
Metabolism and
nutrition disorders
Neoplasms
benign, malignant,
unspecified
Injury, poisoning
and procedural
complications
Psychiatric disorders
Vascular disorders
All
Grades
(%)
Grade
3 or 4
(%)
Diarrhea
Constipation
Nausea
Stomatitis
Vomiting
Abdominal pain
Dyspepsia
Upper respiratory tract
infection
Sinusitis
Skin infection
Pneumonia
Urinary tract infection
Fatigue
Pyrexia
Peripheral edema
Asthenia
Chills
Bruising
Rash
Petechiae
Cough
Oropharyngeal pain
Dyspnea
Musculoskeletal pain
Arthralgia
Muscle spasms
Dizziness
Headache
Peripheral neuropathy
Decreased appetite
63
23
21
21
19
15
13
4
2
2
0
2
0
0
48
21
17
10
10
31
25
23
13
13
54
27
17
19
15
10
27
23
19
21
19
10
17
2
6
6
8
0
4
2
0
4
0
2
0
0
0
0
0
6
0
2
0
2
0
2
Second malignancies*
10*
0
Laceration
10
2
Anxiety
Insomnia
Hypertension
10
10
17
0
0
8
Preferred Term
*One patient death due to histiocytic sarcoma.
Table 4: Treatment-Emergent* Decrease of Hemoglobin, Platelets,
or Neutrophils in Patients with CLL (N=48) in Study 1
Percent of Patients (N=48)
All Grades
Grade 3 or 4
(%)
(%)
Platelets Decreased
71
10
Neutrophils Decreased
54
27
Hemoglobin Decreased
44
0
* Based on laboratory measurements per IWCLL criteria and adverse
reactions
Study 2: 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 Study 2.
Table 5: Non-Hematologic Adverse Reactions ≥ 10% Reported in Study 2
System Organ Class
ADR Term
Gastrointestinal
disorders
Diarrhea
Nausea
Stomatitis*
Constipation
Vomiting
General disorders and
administration site
conditions
Fatigue
Pyrexia
Infections and
infestations
Upper respiratory
tract infection
Pneumonia*
Sinusitis*
Urinary tract infection
Skin and subcutaneous
tissue disorders
Rash*
Petechiae
Bruising*
Musculoskeletal and
connective tissue
disorders
Musculoskeletal Pain*
Arthralgia
Nervous system
disorders
Headache
Dizziness
Injury, poisoning
and procedural
complications
Contusion
Eye disorders
Vision blurred
IMBRUVICA
(N=195)
All
Grade
Grades
3 or 4
(%)
(%)
Ofatumumab
(N=191)
All
Grade
Grades
3 or 4
(%)
(%)
48
26
17
15
14
4
2
1
0
0
18
18
6
9
6
2
0
1
0
1
28
24
2
2
30
15
2
1
16
15
11
10
1
10
1
4
11
13
6
5
2
9
0
1
24
14
12
3
0
0
13
1
1
0
0
0
28
17
2
1
18
7
1
0
14
11
1
0
6
5
0
0
11
0
3
0
10
0
3
0
Subjects with multiple events for a given ADR term are counted once only
for each ADR term.
The system organ class and individual ADR terms are sorted in descending
frequency order in the IMBRUVICA arm.
* Includes multiple ADR terms