;4
Cough 19 0
Epistaxis 11 0
Metabolism and nutrition disorders Decreased appetite 21 2
Dehydration 12 4
Nervous system disorders Dizziness 14 0
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 (%)
* Based on laboratory measurements and adverse reactions
Platelets Decreased 57 17
Neutrophils Decreased 47 29
Hemoglobin Decreased 41 9
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
Body System Adverse Reaction All Grades (%) Grade 3 or 4 (%)
* One patient death due to histiocytic sarcoma.
Gastrointestinal disorders Diarrhea 59 4
Constipation 22 2
Nausea 20 2
Stomatitis 20 |
