ASH Clinical News ACN_5.4s_March_supplement_web - Page 10

IMBRUVICA ® (ibrutinib) IMBRUVICA ® (ibrutinib) Table 11: Adverse Reactions Reported in at Least 10% of Patients and at Least 2% Greater in the IMBRUVICA Arm in Patients with WM in INNOVATE (continued) Body System IMBRUVICA + R Placebo + R Adverse Reaction (N=75) (N=75) All Grades Grade 3 or 4 All Grades Grade 3 (%) (%) (%) or 4 (%) General disorders and administration site conditions Peripheral edema 17 0 12 1 Respiratory, thoracic, and mediastinal disorders Cough 17 0 11 0 Blood and Lymphatic System Disorders Neutropenia* 16 12 11 4 Cardiac Disorders Atrial fibrillation 15 12 3 1 Nervous system disorders Dizziness 11 0 7 0 Psychiatric disorders Insomnia 11 0 4 0 Metabolism and nutrition disorders Hypokalemia 11 0 1 1 Table 12: Non-Hematologic Adverse Reactions in ≥ 10% in Patients with MZL in Study 1121 (N=63) (continued) Body System Adverse Reaction All Grades Grade 3 or 4 (%) (%) Nervous system Dizziness 19 0 disorders Headache 13 0 Psychiatric disorders Anxiety 16 2 The body system and individual ADR preferred terms are sorted in descending frequency order. * Includes multiple ADR terms. The body system and individual ADR preferred terms are sorted in descending frequency order. * Includes multiple ADR terms. Grade 3 or 4 infusion related reactions were observed in 1% of patients treated with IMBRUVICA + R. Study 1121: Adverse reactions and laboratory abnormalities described below in Tables 12 and 13 reflect exposure to IMBRUVICA with a median duration of 11.6 months in Study 1121. Table 12: Non-Hematologic Adverse Reactions in ≥ 10% in Patients with MZL in Study 1121 (N=63) Body System Adverse Reaction All Grades Grade 3 or 4 (%) (%) 5 43 Gastrointestinal Diarrhea 0 25 disorders Nausea 0 19 Dyspepsia 2 17 Stomatitis* 2 16 Abdominal pain 0 14 Constipation 0 13 Abdominal pain upper 2 11 Vomiting 6 44 General disorders and Fatigue 2 24 Peripheral edema administrative site 2 17 Pyrexia conditions 0 41 Skin and subcutaneous Bruising* 5 29 tissue disorders Rash* 0 14 Pruritus 3 40 Musculoskeletal pain* Musculoskeletal and 2 24 Arthralgia connective tissue 3 19 Muscle spasms disorders 0 21 Infections and Upper respiratory infestations tract infection 0 19 Sinusitis* 0 11 Bronchitis 10 11 Pneumonia* 2 16 Metabolism and Decreased appetite 0 16 nutrition disorders Hyperuricemia 0 14 Hypoalbuminemia 0 13 Hypokalemia Vascular disorders Hemorrhage* 30 0 Hypertension* 14 5 Cough 22 2 Respiratory, thoracic Dyspnea 21 2 and mediastinal disorders Table 13: Treatment-Emergent Hematologic Laboratory Abnormalities in Patients with MZL in Study 1121 (N=63) Percent of Patients (N=63) All Grades (%) Grade 3 or 4 (%) Platelets Decreased 49 6 Hemoglobin Decreased 43 13 Neutrophils Decreased 22 13 Chronic Graft versus Host Disease: The data described below reflect exposure to IMBRUVICA in an open-label clinical trial (Study  1129) that included 42 patients with cGVHD after failure of first line corticosteroid therapy and required additional therapy. The most commonly occurring adverse reactions in the cGVHD trial (≥ 20%) were fatigue, bruising, diarrhea, thrombocytopenia, stomatitis, muscle spasms, nausea, hemorrhage, anemia, and pneumonia. Atrial fibrillation occurred in one patient (2%) which was Grade 3. Twenty-four percent of patients receiving IMBRUVICA in the cGVHD trial discontinued treatment due to adverse reactions. The most common adverse reactions leading to discontinuation were fatigue and pneumonia. Adverse reactions leading to dose reduction occurred in 26% of patients. Adverse reactions and laboratory abnormalities described below in Tables 14 and 15 reflect exposure to IMBRUVICA with a median duration of 4.4 months in the cGVHD trial. Table 14: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with cGVHD (N=42) Body System General disorders and administration site conditions Skin and subcutaneous tissue disorders Gastrointestinal disorders Musculoskeletal and connective tissue disorders Vascular disorders Infections and infestations Nervous system disorders Injury, poisoning and procedural complications Respiratory, thoracic and mediastinal disorders Metabolism and nutrition disorders Adverse Reaction Fatigue Pyrexia Edema peripheral Bruising* Rash* Diarrhea Stomatitis* Nausea Constipation Muscle spasms Musculoskeletal pain* All Grades Grade 3 or 4 (%) (%) 12 57 5 17 0 12 40 0 12 0 10 36 2 29 0 26 0 12 29 2 14 5 Hemorrhage* 26 0 Pneumonia* Upper respiratory tract infection Sepsis* Headache 21 19 10 0 10 17 10 5 Fall 17 0 Cough Dyspnea 14 12 0 2 Hypokalemia 12 7 The system organ class and individual ADR preferred terms are sorted in descending frequency order. * Includes multiple ADR terms.