b'NOW APPROVED FOR ADULT PATIENTS WITH WALDENSTRMS MACROGLOBULINEMIA (WM) 1 THE BTK INHIBITOR THAT DELIVERS POWERFUL AND CONSISTENT RESPONSESBRUKINSA (zanubrutinib) is a kinase inhibitor indicated for the treatment of adult patients with Waldenstrms macroglobulinemia. Therst and only head-to-head BRUKINSA Ibrutinib trial of BTK inhibitors in WM*A global, randomized Phase 3 trial in WM across a range of patients 1 Treatment-nave Relapsed/refractory MYD88 MUT (CXCR4 WT , CXCR4 WHIM ) MYD88 WTPowerful Responses Across WM PatientsWhile the primary endpoint of superiority did not reach statistical signi cance, numerically higher VGPR/CR rates were achieved in the BRUKINSA treatment arm.124-hour inhibition of BTK was maintained at 100% in PBMCs and 94% to 100% in lymph nodes when taken at the recommended total daily dose of 320 mg. The clinical significance of 100% inhibition has not been established. 1,2 All patients 1 All patients 1IMPORTANT SAFETY INFORMATION IWWM-6 criteriaModied IWWM-6 criteria (Cohort 1) (Cohort 1)WARNINGS AND PRECAUTIONS BRUKINSA (n=102) Ibrutinib (n=99) BRUKINSA (n=102) Ibrutinib (n=99)Hemorrhage CytopeniasFatal and serious hemorrhagic events have occurredGrade 3 or 4 cytopenias, including neutropenia (26%),embryo-fetal toxicity including malformations78 %78 % 78 %78 %in patients with hematological malignancies treatedthrombocytopenia (11%) and anemia (8%) based onat exposures that were 5 times higher than thoseCR+VGPR+PR CR+VGPR+PR CR+VGPR+PR CR+VGPR+PRwith BRUKINSA monotherapy. Grade 3 or higherlaboratory measurements, were reported in patientsreported in patients at the recommended dose of hemorrhage events including intracranial andtreated with BRUKINSA monotherapy. Grade 4160 mg twice daily. Advise women to avoid becoming(95% CI: 68, 85) (95% CI: 68, 86) (95% CI: 68, 85) (95% CI: 68, 86)gastrointestinal hemorrhage, hematuria andneutropenia occurred in 13% of patients, and Grade 4pregnant while taking BRUKINSA and for 1 week after hemothorax have been reported in 3.4% of patientsthrombocytopenia occurred in 3.6% of patients.the last dose. Advise men to avoid fathering a child16 %7 % 28 %19 %treated with BRUKINSA monotherapy. HemorrhageMonitor complete blood counts regularly duringduring treatment and for 1 week after the last dose.VGPR/CR VGPR/CR VGPR/CR VGPR/CRevents of any grade occurred in 35% of patientstreatment and interrupt treatment, reduce the doseIf this drug is used during pregnancy, or if the patient treated with BRUKINSA monotherapy.or discontinue treatment as warranted. Treat usingbecomes pregnant while taking this drug, the patient Bleeding events have occurred in patientsgrowth factor or transfusions, as needed. should be apprised of the potential hazard to a fetus. 62 % 71 % 49 % 59 %with and without concomitant antiplatelet orSecond Primary Malignancies ADVERSE REACTIONS PR PR PR PRanticoagulation therapy. Co-administration ofSecond primary malignancies, including non-skin BRUKINSA with antiplatelet or anticoagulantcarcinoma, have occurred in 14% of patients treatedThe most common adverse reactions, including medications may further increase the risk oflaboratory abnormalities, in 30% of patientsMedian follow-up time was 19.4 months.hemorrhage. with BRUKINSA monotherapy. The most frequentwho received BRUKINSA (N=847) included decreased3 1second primary malignancy was non-melanoma skinneutrophil count (54%), upper respiratory tractThe prespeci ed ecacy outcome measure of VGPR/CR was assessed by IRC.Monitor for signs and symptoms of bleeding.cancer reported in 8% of patients. Other second primaryinfection (47%), decreased platelet count (41%), Discontinue BRUKINSA if intracranial hemorrhagemalignancies included malignant solid tumors (4.0%),hemorrhage (35%), decreased lymphocyte count of any grade occurs. Consider the benefit-riskmelanoma (1.7%) and hematologic malignancies (1.2%).(31%), rash (31%) and musculoskeletal pain (30%).of withholding BRUKINSA for 3-7 days pre- andAdvise patients to use sun protection, and monitorSafety in WM is consistent with the established BRUKINSA pro le1post-surgery depending upon the type ofpatients for the development of second primaryDRUG INTERACTIONSsurgery and the risk of bleeding. malignancies. CYP3A Inhibitors: When BRUKINSA is co-administeredSerious adverse reactions, including fatal events, have occurred with BRUKINSA, including hemorrhage, infections, Infections Cardiac Arrhythmiaswith a strong CYP3A inhibitor, reduce BRUKINSAcytopenias, second primary malignancies, and cardiac arrhythmias. The most common adverse reactions (30%) Fatal and serious infections (including bacterial,Atrial fibrillation and atrial flutter were reported indose to 80 mg once daily. For co-administrationinclude neutrophil count decreased, upper respiratory tract infection, platelet count decreased, hemorrhage, viral, or fungal) and opportunistic infections3.2% of patients treated with BRUKINSA monotherapy.with a moderate CYP3A inhibitor, reduce BRUKINSAlymphocyte count decreased, rash, and musculoskeletal pain.have occurred in patients with hematologicalPatients with cardiac risk factors, hypertension anddose to 80 mg twice daily.*Patients were enrolled from the United States, Europe, and Australia/New Zealand. BTK=Brutons tyrosine kinase; CI=con dence interval; CR=complete response; IRC=independent review committee; IWWM-6=6th International malignancies treated with BRUKINSA monotherapy.acute infections may be at increased risk. Grade 3CYP3A Inducers: Avoid co-administration withIWWM-6 criteria (Owen et al, 2013) requires complete resolution of extramedullary disease (EMD) if present at baseline for VGPR to be assessed.Workshop on Waldenstrms Macroglobulinemia; MUT=mutated; ORR=overall response rate; PBMCs=peripheral blood mononuclear cells; Grade 3 or higher infections occurred in 27% ofor higher events were reported in 1.1% of patientsModi ed IWWM-6 criteria (Treon, 2015) requires a reduction in EMD if present at baseline for VGPR to be assessed. PR=partial response; VGPR=very good partial response; WHIM=WHIM syndrome-like somatic mutation; WT=wild type. patients, most commonly pneumonia. Infections duetreated with BRUKINSA monotherapy. Monitor signsmoderate or strong CYP3A inducers. There were no CRs in either treatment arm. 4,5to hepatitis B virus (HBV) reactivation have occurred.and symptoms for atrial fibrillation and atrial flutterSPECIFIC POPULATIONSand manage as appropriate. References: 1. BRUKINSA. Package insert. BeiGene, Ltd; 2021. 2. Tam C, Trotman J, Opat S, et al. Phase 1 study of the selective BTK inhibitor zanubrutinib Consider prophylaxis for herpes simplex virus,Hepatic Impairment: The recommended dose ofin B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019;134(11):851-859. 3. Tam CS, Opat S, DSa S, et al. A randomized phase 3 trial pneumocystis jiroveci pneumonia and otherEmbryo-Fetal Toxicity BRUKINSA for patients with severe hepatic impairmentof zanubrutinib vs ibrutinib in symptomatic Waldenstrm macroglobulinemia: the ASPEN study. Blood . 2020;136(18):2038-2050. 4. Owen RG, Kyle RA, infections according to standard of care in patientsBased on findings in animals, BRUKINSA can causeis 80 mg orally twice daily. Stone MJ, et al. Response assessment in Waldenstrm macroglobulinemia: update from the VIth International Workshop.Br J Haematol.who are at increased risk for infections. Monitorfetal harm when administered to a pregnant woman.2013;160(2):171-176. 5. Treon SP. How I treat Waldenstrm macroglobulinemia. Blood. 2015;126(6):721-732.and evaluate patients for fever or other signs andAdministration of zanubrutinib to pregnant ratsPlease see Brief Summary of full PrescribingBRUKINSA and BeiGene are registered trademarks owned by BeiGene, Ltd. symptoms of infection and treat appropriately.during the period of organogenesis causedInformation on following pages.BeiGene, Ltd. 2021 All Rights Reserved. 0821-BRU-PRC-032-r1 10/2021 LEARN MORE AT BRUKINSA.com22065_2_WM_HCPJournalAd_Fed_Pract_7-875x10-75_RL.indd 1-2 11/2/21 5:00 PM'