ASH Clinical News ACN_4.14_Full Issue_web | Page 67

RESONATE TM -2 FRONTLINE DATA RESONATE TM -2 was a multicenter, randomized 1:1, open-label, Phase 3 trial of IMBRUVICA® vs chlorambucil in frontline CLL/SLL patients ≥65 years (N=269) 2,3 Patients with 17p deletion were excluded 3 EXTENDED OVERALL SURVIVAL 2 PROLONGED PROGRESSION-FREE SURVIVAL 2,3 • Median follow-up was 28 months 2 • Fewer deaths with IMBRUVICA® were observed; 11 (8.1%) in the IMBRUVICA® arm vs 21 (15.8%) in the chlorambucil arm 2 • Median follow-up was 18 months 3 • With IMBRUVICA®, median PFS was not estimable vs 18.9 months (95% CI: 14.1, 22.0) with chlorambucil 2 • PFS and ORR (CR and PR) were assessed by an IRC according to the revised 2008 iwCLL criteria 3 SECONDARY ENDPOINT: OS IMBRUVICA® vs CHLORAMBUCIL PRIMARY ENDPOINT: PFS IMBRUVICA® vs CHLORAMBUCIL RESONATE™-2 Adverse Reactions ≥15% • Diarrhea (42%) • Musculoskeletal pain (36%) • Cough (22%) • Rash (21%) • Bruising (19%) • Peripheral edema (19%) Embryo-Fetal Toxicity: Based on fi ndings in animals, IMBRUVICA ® can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA ® and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Advise men to avoid fathering a child during the same time period. ADVERSE REACTIONS The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were thrombocytopenia (58%)*, neutropenia (58%)*, diarrhea (42%), anemia (39%)*, rash (31%), musculoskeletal pain (31%), bruising (31%), nausea (28%), fatigue (27%), hemorrhage (23%), and pyrexia (20%). The most common Grade 3 or 4 adverse reactions (≥5%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia (36%)*, thrombocytopenia (15%)*, and pneumonia (10%). Approximately 7% of patients discontinued IMBRUVICA ® due to adverse reactions. Adverse reactions leading to discontinuation included hemorrhage (1.2%), atrial fi brillation (1.0%), pneumonia (1.0%), rash (0.7%), diarrhea (0.6%), neutropenia (0.6%), sepsis (0.5%), interstitial lung disease (0.3%), bruising (0.2%), non-melanoma skin cancer (0.2%), and thrombocytopenia (0.2%). Eight percent of patients had a dose reduction due to adverse reactions. * Treatment-emergent decreases (all grades) were based on laboratory measurements and adverse reactions. To learn more, visit IMBRUVICAHCP.com • Pyrexia (17%) • Dry eye (17%) • Arthralgia (16%) • Skin infection (15%) DRUG INTERACTIONS CYP3A Inhibitors: Dose adjustments may be recommended. CYP3A Inducers: Avoid coadministration with strong CYP3A inducers. SPECIFIC POPULATIONS Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA ® in patients with severe baseline hepatic impairment. In patients with mild or moderate impairment, reduce IMBRUVICA ® dose. Please see the Brief Summary on the following pages. CI=confi dence interval, CLL=chronic lymphocytic leukemia, HR=hazard ratio, IRC=Independent Review Committee, iwCLL=International Workshop on CLL, OS=overall survival, PFS=progression-free survival, SLL=small lymphocytic lymphoma. References: 1. Data on fi le. Pharmacyclics LLC. 2. IMBRUVICA ® (ibrutinib) Prescribing Information. Pharmacyclics LLC 2018. 3. Burger JA, Tedeschi A, Barr PM, et al; for the RESONATE-2 Investigators. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425-2437.