b'B:8.125"T:7.875"S:7.375"Start with IMBRUVICA in 1L CLL 1L I V I N GL O N G E RW I T H O U TP R O G R E S S I O NSuperior PFS: IMBRUVICA + rituximab vs FCR in E1912 189% (95% CI: 85, 92) estimated PFS rate with IMBRUVICA + rituximabat 3 years vs 70% (95% CI: 61, 78) with FCR in patients 70 years old 1,2HR=0.34 (95% CI: 0.22, 0.52; P 1,30.0001) (primary endpoint)CLL/ IMBRUVICA (ibrutinib) is a kinase inhibitor indicated for the treatment of adult patients with:SLLChronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL). 1L=frontline, CI=confi dence interval, FCR=fl udarabine, cyclophosphamide, and rituximab, HR=hazard ratio, PFS=progression-free survival.Visit IMBRUVICAHCP.com to learn moreTumor Lysis Syndrome: Tumor lysis syndrome has been infrequentlyDRUG INTERACTIONSreported with IMBRUVICA. Assess the baseline risk (e.g., high tumorCYP3A Inhibitors: Co-administration of IMBRUVICA with strong burden) and take appropriate precautions. or moderate CYP3A inhibitors may increase ibrutinib plasma Monitor patients closely and treat as appropriate. concentrations. Dose modifi cations of IMBRUVICA may beS:10.25" T:10.75" B:11"Embryo-Fetal Toxicity: Based on fi ndings in animals, IMBRUVICArecommended when used concomitantly with posaconazole, can cause fetal harm when administered to a pregnant woman.voriconazole, and moderate CYP3A inhibitors. Avoid concomitant Advise pregnant women of the potential risk to a fetus. Adviseuse of other strong CYP3A inhibitors. Interrupt IMBRUVICA if females of reproductive potential to use effective contraceptionstrong inhibitors are used short-term (e.g., for7 days).during treatment with IMBRUVICA and for 1 month after the lastSee dose modifi cation guidelines in USPI sections 2.3 and 7.1.dose. Advise males with female partners of reproductive potential toCYP3A Inducers: Avoid coadministration with strong CYP3A inducers.use effective contraception during the same time period. SPECIFIC POPULATIONSADVERSE REACTIONS Hepatic Impairment (based on Child-Pugh criteria): Avoid use of The most common adverse reactions (30%) in patients with B-cellIMBRUVICA in patients with severe baseline hepatic impairment. In malignancies (MCL, CLL/SLL, WM and MZL) werepatients with mild or moderate impairment, reduce recommended thrombocytopenia (54.5%)*, diarrhea (43.8%), fatigue (39.1%),IMBRUVICA dose and monitor more frequently for adverse reactions musculoskeletal pain (38.8%), neutropenia (38.6%)*, rash (35.8%),of IMBRUVICA.anemia (35.0%)*, and bruising (32.0%). Please see Brief Summary on the following pages.The most common Grade3 adverse reactions (5%) in patientsReferences: 1. IMBRUVICA (ibrutinib) Prescribing Information. with B-cell malignancies (MCL, CLL/SLL, WM and MZL) werePharmacyclics LLC. 2. Data on fi le. Pharmacyclics LLC. neutropenia (20.7%)*, thrombocytopenia (13.6%)*,3. Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab pneumonia (8.2%), and hypertension (8.0%). or chemoimmunotherapy for chronic lymphocytic leukemia. Approximately 9% (CLL/SLL), 14% (MCL), 14% (WM) andN Engl J Med. 2019;381(5):432-443.10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4-10% (CLL/SLL), 9% (MCL), and 7% (WM [5%] and MZL [13%]) of patients discontinued due to adverse reactions. * Treatment-emergent decreases (all grades) were based on laboratory measurements. Pharmacyclics LLC 2020 Janssen Biotech, Inc. 202010/20 PRC-07105aDate: October 21, 2020 11:39 AM Brand: IMBRUVICAColors: CMYKFile Name: PRC-07105a_853809_v1 Size: 7.875" x 10.75"page2 Right Hand Page 100, 0, 0, 35 =Customer Code: PRC-07105a Description: Living Longer Without Progression 54, 0, 100, 0 =We Are Alexander #: 853809 Pub: US Medicine 2021 Directory 99, 14, 3, 0 ='