ASH Clinical News Focus on Myeloid Malignancies | Page 29

IMBRUVICA ® (ibrutinib) capsules IMBRUVICA ® (ibrutinib) capsules
Table 2: Treatment-Emergent* Decrease of Hemoglobin, Platelets, or
Neutrophils in Patients with MCL (N=111)
Percent of Patients (N=111)
All Grades
Grade 3 or 4
(%)
(%)
Platelets Decreased
57
17
Neutrophils Decreased
47
29
Hemoglobin Decreased
41
9
* Based on laboratory measurements and adverse reactions Table 3: Non-Hematologic Adverse Reactions in ≥ 10% of Patients
with CLL/SLL (N=51) in Study 1 (continued)
All Grades Grade 3 or 4
Body System
Adverse Reaction
(%)
(%)
Metabolism and
Decreased appetite
16
2
nutrition disorders
Neoplasms
Second
12*
0
benign, malignant,
malignancies*
unspecified
Vascular disorders
Hypertension
16
8
* One patient death due to histiocytic sarcoma.
Ten patients (9%) discontinued treatment due to adverse reactions in the
trial (N=111). The most frequent adverse reaction leading to treatment
discontinuation was subdural hematoma (1.8%). Adverse reactions leading
to dose reduction occurred in 14% of patients.
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/Small Lymphocytic Lymphoma: The data
described below reflect exposure in one single-arm, open-label clinical
trial and three randomized controlled clinical trials in patients with
CLL/SLL (n=1278 total and n=668 patients exposed to IMBRUVICA). Study 1
included 51 patients with previously treated CLL/SLL, Study 2 included 391
randomized patients with previously treated CLL or SLL who received single
agent IMBRUVICA or ofatumumab, Study 3 included 269 randomized patients
65 years or older with treatment naïve-CLL or SLL who received single
agent IMBRUVICA or chlorambucil and Study 4 included 578 randomized
patients with previously treated CLL or SLL who received IMBRUVICA in
combination with bendamustine and rituximab or placebo in combination
with bendamustine and rituximab.
The most commonly occurring adverse reactions in Studies 1, 2, 3 and 4
in patients with CLL/SLL receiving IMBRUVICA (≥ 20%) were neutropenia,
thrombocytopenia, anemia, diarrhea, musculoskeletal pain, nausea, rash,
bruising, fatigue, pyrexia and hemorrhage. Four to 10 percent of patients
receiving IMBRUVICA in Studies 1, 2, 3 and 4 discontinued treatment due
to adverse reactions. These included pneumonia, hemorrhage, atrial
fibrillation, rash and neutropenia (1% each). Adverse reactions leading to
dose reduction occurred in approximately 6% of patients.
Study 1: Adverse reactions and laboratory abnormalities from the CLL/SLL
trial (N=51) using single agent IMBRUVICA 420 mg daily in patients with
previously treated CLL/SLL occurring at a rate of ≥ 10% with a median duration
of treatment of 15.6 months are presented in Tables 3 and 4.
Table 3: Non-Hematologic Adverse Reactions in ≥ 10% of Patients
with CLL/SLL (N=51) in Study 1
All Grades Grade 3 or 4
Body System
Adverse Reaction
(%)
(%)
Gastrointestinal
Diarrhea
59
4
disorders
Constipation
22
2
Nausea
20
2
Stomatitis
20
0
Vomiting
18
2
Abdominal pain
14
0
Dyspepsia
12
0
Infections and
Upper respiratory
infestations
tract infection
47
2
Sinusitis
22
6
Skin infection
16
6
Pneumonia
12
10
Urinary tract infection
12
2
General disorders and Fatigue
33
6
administration site
Pyrexia
24
2
conditions
Peripheral edema
22
0
Asthenia
14
6
Chills
12
0
Skin and
Bruising
51
2
subcutaneous tissue
Rash
25
0
disorders
Petechiae
16
0
Respiratory, thoracic
Cough
22
0
and mediastinal
Oropharyngeal pain
14
0
disorders
Dyspnea
12
0
Musculoskeletal and
Musculoskeletal pain
25
6
connective tissue
Arthralgia
24
0
disorders
Muscle spasms
18
2
Nervous system
Dizziness
20
0
disorders
Headache
18
2
Table 4: Treatment-Emergent* Decrease of Hemoglobin, Platelets,
or Neutrophils in Patients with CLL/SLL (N=51) in Study 1
Platelets Decreased
Neutrophils Decreased
Hemoglobin Decreased
Percent of Patients (N=51)
All Grades (%)
Grade 3 or 4 (%)
69
12
53
26
43
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 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 Study 2
IMBRUVICA
Ofatumumab
(N=195)
(N=191)
Body System
All Grades Grade 3 or 4 All Grades Grade 3 or 4
Adverse Reaction
(%)
(%)
(%)
(%)
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
16
1
11
2
infection
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