ASH Clinical News April 2016 | Page 5

UP FRONT American Society of Clinical Oncology Annual Meeting June 3 – 8, 2016 Chicago, IL ASCO brings together 30,000 oncology professionals from around the world, with educational sessions on new therapies and the latest ground-breaking research. European Hematology Association Annual Congress June 9 – 12, 2016 Copenhagen, Denmark The 21st Annual Congress will provide a forum for sharing clinical and translational research in hematologic disorders and disseminating evidence-based knowledge. ASH Meeting on Lymphoma Biology June 18 – 21, 2016 Colorado Springs, CO The ASH Meeting on Lymphoma Biology brings together experts from around the world to discuss the latest breakthroughs in basic and translational lymphoma research, address current challenges in the field, and exchange ideas on how to move the field forward. ASH Workshop on Genome Editing July 14 – 15, 2016 Washington, DC The ASH Workshop on Genome Editing provides a forum that focuses specifically on the mechanistic aspects and possible clinical applications of this technology to blood disorders, as well as a platform for the exchange of ideas between academic researchers, industry scientists, and regulators involved in the clinical application of genome editing technology. International Society of Experimental Hematology 45th Annual Scientific Meeting The kidney is a route of excretion for monomethyl auristatin E (MMAE). The pharmacokinetics and safety of The The kidney kidneyisisaaroute routeofofexcretion excretionfor formonomethyl monomethylauristatin auristatinEE(MMAE). (MMAE).The Thepharmacokinetics pharmacokineticsand andsafety safetyofof vedotin and and MMAE MMAE were were evaluated evaluated after after the the administration administration of 1.2 1.2 mg/kg mg/kg of ADCETRIS ADCETRIS to to patients patients brentuximab vedotin brentuximab brentuximabvedotin and MMAE were evaluated after the administration ofof1.2 mg/kg ofofADCETRIS to patients with mild (CLcr (CLcr >50-80 >50-80 mL/min; mL/min; n=4), n=4), moderate moderate (CLcr (CLcr 30-50 30-50 mL/min; mL/min; n=3) n=3) and and severe severe (CLcr (CLcr <30 <30 mL/min; mL/min; withmild mild with (CLcr >50-80 mL/min; n=4), moderate (CLcr 30-50 mL/min; n=3) and severe (CLcr <30 mL/min; n=3) renal impairment. In patients with severe renal impairment, the rate of Grade 3 or worse adverse n=3)renal renalimpairment. impairment.InInpatients patientswith withsevere severerenal renalimpairment, impairment,the therate rateofofGrade Grade33or orworse worseadverse adverse n=3) reactions was 3/3 (100%) compared 3/8 (38%) patients with normal renal function. Additionally, the reactionswas was3/3 3/3(100%) (100%)compared comparedtoto to3/8 3/8(38%) (38%)inin inpatients patientswith withnormal normalrenal renalfunction. function.Additionally, Additionally,the the reactions AUC MMAE (component ADCETRIS) was approximately 2-fold higher patients with severe renal AUCofof ofMMAE MMAE(component (componentofof ofADCETRIS) ADCETRIS)was wasapproximately approximately2-fold 2-foldhigher higherinin inpatients patientswith withsevere severerenal renal AUC impairment compared to patients with normal renal function. Due to higher MMAE exposure, ≥Grade 3 impairment compared to patients with normal renal function. Due to higher MMAE exposure, ≥Grade 3 impairment compared to patients with normal renal function. Due to higher MMAE exposure, ≥Grade 3 adverse reactions may be more frequent patients with severe renal impairment compared patients with adversereactions reactionsmay maybe bemore morefrequent frequentinin inpatients patientswith withsevere severerenal renalimpairment impairmentcompared comparedtoto topatients patientswith with adverse normal renal function. normalrenal renalfunction. function. normal Hepatic Impairment HepaticImpairment Impairment Hepatic Avoid the use ADCETRIS patients with moderate severe hepatic impairment. Avoidthe theuse useofof ofADCETRIS ADCETRISinin inpatients patientswith withmoderate moderateoror orsevere severehepatic hepaticimpairment. impairment. Avoid The liver route clearance for MMAE. The pharmacokinetics and safety brentuximab vedotin and Theliver liverisis isaaaroute routeofof ofclearance clearancefor forMMAE. MMAE.The Thepharmacokinetics pharmacokineticsand andsafety safetyofof ofbrentuximab brentuximabvedotin vedotinand and The MMAE were evaluated afterthe theadministration administrationofof of1.2 1.2mg/kg mg/kgofof ofADCETRIS ADCETRIStoto topatients patientswith withmild mild(Child-Pugh (Child-PughA;A; A; MMAEwere wereevaluated evaluatedafter after the administration 1.2 mg/kg ADCETRIS patients with mild (Child-Pugh MMAE n=1), moderate (Child-Pugh B; n=5) and severe (Child-Pugh C; n=1) hepatic impairment. In patients with n=1),moderate moderate(Child-Pugh (Child-PughB;B;n=5) n=5)and andsevere severe(Child-Pugh (Child-PughC;C;n=1) n=1)hepatic hepaticimpairment. impairment.InInpatients patientswith with n=1), moderate or severe hepatic impairment, the rate of ≥Grade 3 adverse reactions was 6/6 (100%) compared moderateororsevere severehepatic hepaticimpairment, impairment,the therate rateofof≥Grade moderate ≥Grade33adverse adversereactions reactionswas was6/6 6/6(100%) (100%)compared compared 3/8 (38%) patients with normal hepatic function. Additionally, the AUC MMAE was approximately to3/8 3/8(38%) (38%)inin inpatients patientswith withnormal normalhepatic hepaticfunction. function.Additionally, Additionally,the theAUC AUCofof ofMMAE MMAEwas wasapproximately approximately toto 2.2-fo