ASH Clinical News ACN_4.4_SUPP_Digital Version | Page 35

IMBRUVICA ® (ibrutinib) capsules
Table 1: Non-Hematologic Adverse Reactions in ≥ 10% of Patients
with MCL (N=111) (continued)
Grade 3
All
or 4
Grades
(%)
(%)
Body System
Adverse Reaction
Metabolism and
Decreased appetite
21
2
nutrition disorders
Dehydration
12
4
Nervous system
Dizziness
14
0
disorders
Headache
13
0
Table 2: Treatment-Emergent* Hematologic Laboratory Abnormalities
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
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 (Study 1102) and three randomized controlled clinical trials (RESONATE,
RESONATE-2, and HELIOS) in patients with CLL/SLL (n=1278 total and n=668
patients exposed to IMBRUVICA). Study 1102 included 51 patients with
previously treated CLL/SLL, RESONATE included 391 randomized patients
with previously treated CLL or SLL who received single agent IMBRUVICA
or ofatumumab, RESONATE-2 included 269 randomized patients 65 years or
older with treatment naïve-CLL or SLL who received single agent IMBRUVICA
or chlorambucil, and HELIOS 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 1102, RESONATE,
RESONATE-2, and HELIOS 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 1102, RESONATE,
RESONATE-2, and HELIOS 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 1102: 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 1102
All
Grade 3
Grades
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