b'IMBRUVICA (ibrutinib)IMBRUVICA (ibrutinib) Table 8: Adverse Reactions Reported in at Least 10% of Patients in theTable 9: Adverse Reactions Reported in at Least 15% of Patients in the IMBRUVICA Arm in Patients with CLL/SLL in iLLUMINATE (continued) IMBRUVICA Arm in Patients with CLL/SLL in E1912 (continued)IMBRUVICA +Chlorambucil +Fludarabine + Obinutuzumab Obinutuzumab IMBRUVICA +Cyclophosphamide (N=113) (N=115) Rituximab + Rituximab AllGrade 3AllGrade 3(N=352) (N=158)Body System Grades or HigherGradesor HigherAllGrade 3AllGrade 3 Adverse Reaction (%) (%) (%) (%) Body System Grades or HigherGradesor Higher Gastrointestinal disorders Adverse Reaction (%) (%) (%) (%) Diarrhea 34 3 10 0 Musculoskeletal andConstipation 16 0 12 1 connective tissue disorders Nausea 12 0 30 0Musculoskeletal pain* 61 5 35 2Musculoskeletal and Arthralgia 41 5 10 1connective tissue disorders Gastrointestinal disorders Musculoskeletal pain* 33 1 23 3Diarrhea 53 4 27 1 Arthralgia 22 1 10 0Nausea 40 1 64 1 Muscle spasms 13 0 6 0Stomatitis* 22 1 8 1Respiratory, thoracic and Abdominal pain* 19 2 10 1mediastinal disordersVomiting 18 2 28 0 Cough 27 1 12 0Constipation 17 0 32 0Injury, poisoning andSkin and subcutaneous tissue procedural complications disordersInfusion related reaction 25 2 58 8Rash* 49 4 29 5Vascular disordersBruising* 36 1 4 1 Hemorrhage* 25 1 9 0 Vascular disorders Hypertension* 17 4 4 3Hypertension* 42 19 22 6General disorders and Hemorrhage* 31 2 8 1administration site conditions Nervous system disorders Pyrexia 19 2 26 1Headache 40 1 27 1 Fatigue 18 0 17 2Dizziness 21 1 13 1 Peripheral edema 12 0 7 0Peripheral neuropathy* 19 1 13 1Infections and infestations Respiratory, thoracic andPneumonia* 16 9 9 4 mediastinal disordersUpper respiratory tract 14 1 6 0Cough 32 0 25 0infection Dyspnea 22 2 21 1 Skin infection* 13 1 3 0 Infections and infestations Urinary tract infection 12 3 7 1 Upper respiratory tract 29 1 19 2 Nasopharyngitis 12 0 3 0 infectionConjunctivitis 11 0 2 0Skin infection* 16 1 3 1Metabolism and nutritionMetabolism and nutrition disorders disorders Hyperuricemia 13 1 0 0Hyperuricemia 19 1 4 0Cardiac disordersDecreased appetite 15 0 20 1 Atrial fibrillation 12 5 0 0 Psychiatric disordersPsychiatric disordersInsomnia 16 1 19 1 Insomnia 12 0 4 0 The body system and individual ADR terms are sorted in descending frequency The body system and individual ADR terms are sorted in descending frequencyorder in the IMBRUVICA arm.order in the IMBRUVICA arm. * Includes multiple ADR terms* Includes multiple ADR terms Includes one event with a fatal outcome.Table 10: Select Laboratory Abnormalities ( 15% Any Grade), New or E1912: Adverse reactions described below in Table 9 reflect exposure toWorsening from Baseline in Patients Receiving IMBRUVICA (E1912)IMBRUVICA + rituximab with a median duration of 34.3 months and exposureFludarabine + to FCR with a median of 4.7 months in E1912 in patients with previouslyIMBRUVICA +Cyclophosphamide + untreated CLL/SLL who were 70 years or younger.RituximabRituximab Table 9: Adverse Reactions Reported in at Least 15% of Patients in the(N=352) (N=158)IMBRUVICA Arm in Patients with CLL/SLL in E1912 AllGrade AllGradeFludarabine +Grades 3 or 4 Grades3 or 4IMBRUVICA +Cyclophosphamide(%) (%) (%) (%)Rituximab + RituximabHematology abnormalities(N=352) (N=158)Neutrophils decreased 53 30 70 44AllGrade 3AllGrade 3 Body System Grades or HigherGradesor Higher Platelets decreased 43 7 69 25Adverse Reaction (%) (%) (%) (%)Hemoglobin decreased 26 0 51 2General disorders andChemistry abnormalitiesadministration site conditions Fatigue 80 2 78 3Creatinine increased 38 1 17 1 Peripheral edema 28 1 17 0Bilirubin increased 30 2 15 0 Pyrexia 27 1 27 1AST increased 25 3 23 1 Pain 23 2 8 0 Based on laboratory measurements per IWCLL criteria'