ASH Clinical News ACN_5.4s_March_supplement_web - Page 9

IMBRUVICA ® (ibrutinib) IMBRUVICA ® (ibrutinib) Table 8: Adverse Reactions Reported in at Least 10% of Patients and at Least 2% Greater in the IMBRUVICA Arm in Patients with CLL/SLL in HELIOS (continued) Ibrutinib + BR Placebo + BR (N=287) (N=287) All Grades Grade 3 or 4 All Grades Grade 3 or 4 (%) (%) (%) (%) Body System Adverse Reaction Vascular disorders Hemorrhage* 19 2 9 1 Hypertension* 11 5 5 2 Infections and infestations Bronchitis 13 2 10 3 Skin infection* 10 3 6 2 Metabolism and nutrition disorders Hyperuricemia 10 2 6 0 The body system and individual ADR terms are sorted in descending frequency order in the IMBRUVICA arm. * Includes multiple ADR terms <1 used for frequency above 0 and below 0.5% Atrial fibrillation of any grade occurred in 7% of patients treated with IMBRUVICA  +  BR and 2% of patients treated with placebo + BR. The frequency of Grade 3 and 4 atrial fibrillation was 3% in patients treated with IMBRUVICA + BR and 1% in patients treated with placebo +BR. Waldenström’s Macroglobulinemia and Marginal Zone Lymphoma: The data described below reflect exposure to IMBRUVICA in three single-arm open- label clinical trials (Study 1118, Study 1121, and INNOVATE monotherapy arm) and one randomized controlled trial (INNOVATE) in patients with WM or MZL, including a total n=307 patients overall and n=232 patients exposed to IMBRUVICA. Study 1118 included 63 patients with previously treated WM who received single agent IMBRUVICA. Study 1121 included 63 patients with previously treated MZL who received single agent IMBRUVICA. INNOVATE included 150 patients with treatment naïve or previously treated WM who received IMBRUVICA or placebo in combination with rituximab. The INNOVATE monotherapy arm included 31 patients with previously treated WM who failed prior rituximab-containing therapy and received IMBRUVICA. The most commonly occurring adverse reactions in Studies 1118, 1121, and INNOVATE (≥ 20%) were thrombocytopenia, diarrhea, bruising, neutropenia, musculoskeletal pain, hemorrhage, anemia, rash, fatigue, and nausea. Seven percent of patients receiving IMBRUVICA across Studies 1118, 1121, and INNOVATE discontinued treatment due to adverse reactions. The most common adverse reactions leading to discontinuation were atrial fibrillation, interstitial lung disease, diarrhea and rash. Adverse reactions leading to dose reduction occurred in 13% of patients. Study 1118 and INNOVATE Monotherapy Arm: Adverse reactions and laboratory abnormalities described below in Tables 9 and 10 reflect exposure to IMBRUVICA with a median duration of 11.7 months in Study 1118 and 33 months in the INNOVATE Monotherapy Arm. Table 9: Non-Hematologic Adverse Reactions in ≥ 10% in Patients with WM in Study 1118 and the INNOVATE Monotherapy Arm (N=94) All Grades Grade 3 or 4 Body System Adverse Reaction (%) (%) 2 38 Gastrointestinal Diarrhea 0 21 disorders Nausea 0 15 Stomatitis* 1 12 Constipation 0 12 Gastroesophageal reflux disease Skin and subcutaneous Bruising* 28 1 tissue disorders Rash* 21 1 Vascular disorders Hemorrhage* 28 0 Hypertension* 14 4 18 2 General disorders and Fatigue Pyrexia 12 2 administrative site conditions Musculoskeletal pain* 21 0 Musculoskeletal and Muscle spasms 19 0 connective tissue disorders Table 9: Non-Hematologic Adverse Reactions in ≥ 10% in Patients with WM in Study 1118 and the INNOVATE Monotherapy Arm (N=94) (continued) Body System Infections and infestations Nervous system disorders Respiratory, thoracic and mediastinal disorders Adverse Reaction Upper respiratory tract infection Skin infection* Sinusitis* Pneumonia* Headache Dizziness Cough All Grades (%) 19 Grade 3 or 4 (%) 0 18 16 13 14 13 13 3 0 5 0 0 0 The body system and individual ADR preferred terms are sorted in descending frequency order. * Includes multiple ADR terms. Table 10: Treatment-Emergent Hematologic Laboratory Abnormalities in Patients with WM in Study 1118 and the INNOVATE Monotherapy Arm (N=94) Platelets Decreased Neutrophils Decreased Hemoglobin Decreased Percent of Patients (N=94) All Grades (%) Grade 3 or 4 (%) 38 11 43 16 21 6 INNOVATE: Adverse reactions described below in Table 11 reflect exposure to IMBRUVICA + R with a median duration of 25.8 months and exposure to placebo + R with a median duration of 15.5 months in patients with treatment naïve or previously treated WM in INNOVATE. 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 Body System IMBRUVICA + R Placebo + R Adverse Reaction (N=75) (N=75) All Grades Grade 3 or 4 All Grades Grade 3 (%) (%) (%) or 4 (%) Skin and subcutaneous tissue disorders Bruising* 37 1 5 0 Rash* 24 1 11 0 Musculoskeletal and connective tissue disorders Musculoskeletal 35 4 21 3 pain* Arthralgia 24 3 11 1 Muscle spasms 17 0 12 1 Vascular disorders Hemorrhage* 32 3 17 3 Hypertension* 20 13 5 4 Gastrointestinal disorders Diarrhea 28 0 15 1 Nausea 21 0 12 0 Dyspepsia 16 0 1 0 Constipation 13 1 11 1 Infections and infestations Pneumonia* 19 13 5 3 Skin infection* 17 3 3 0 Urinary tract infection 13 0 0 0 Bronchitis 12 3 7 0 Influenza 12 0 7 1 Viral upper respiratory 11 0 7 0 tract infection