b'VENCLEXTA + GAZYVA (obinutuzumab) DELIVERS DURABLE PROGRESSION-FREE SURVIVAL 1,2CHEMO-FREE TREATMENT WITH THE % VEN+G reduced the risk of progression After a median follow-up of 28 months (range: 0.136 months)1:67 or death by 67% vs GClb (HR=0.33; \x7fMedian PFS was not reached in either armThere were 29 events (14 progression and 15 death events) in the \x7fSTRENGTH *TO STOP risk reduction 95% CI: 0.220.51 [P0.0001]) VEN+G arm compared with 79 in the GClb arm (71 progression andIRC-assessed PFS (primary endpoint)1 8 death events)Number of events based on earliest event of disease progression or death due to any cause. Events due to progression may include deaths occurring post-progression.RATES OF RESPONSE AND UNDETECTABLE MRD (u MRD) 1AFTER 12 MONTHS IN 1L CLLSelect secondary endpoints 1,3,41INV-assessed response rates for VEN+G vs GClb, respectivelyCR+CRi: 50% (n=107/216) vs 23% (n=50/216)\x7f* CLL14 was a randomized (1:1), multicenter, actively controlled, open-label phase 3 study that evaluated the efficacy and safety of VEN+G versus GClb for previously untreated CLL in 432 patients with coexisting medical conditions (total Cumulative Illness Rating Scale [CIRS] uMRD rates in ITT populationUndetectable MRD in peripheral blood (ITT population) was 76% (n=163/216) in VEN+G patients (95% CI: 6981), compared with 35% (n=76/216) in score 6 or creatinine clearance 70 mL/min). The primary endpoint was IRC-assessed PFS. VEN+G significantly reduced the risk of death \x7for progression by 67% vs GAZYVA + chlorambucil (HR=0.33; 95% CI: 0.220.51 [P0.0001]). After a median follow-up of 28 months GClb patients (95% CI: 2942)(range: 0.136 months), median PFS was not reached in either arm.In patients with CR, the rate of undetectable MRD in peripheral blood was 87% (n=87/100) for VEN+G (95% CI: 7993) and 62% (n=29/47) forThe VEN+G regimen is designed to be completed after 12 months (twelve 28-day treatment cycles): GAZYVA is administered in Cycles 16, GClb (95% CI: 4675)# and VENCLEXTA is taken orally 400 mg/day from Cycle 3, Day 1, after the first cycle of GAZYVA and the 5-week VENCLEXTA dose ramp-up. Rates of uMRD in peripheral blood in evaluable patientsUndetectable MRD in peripheral blood of evaluable VEN+G patients was 87% (n=163/187) compared with 42% (n=76/182) in the GClb arm4\x7f\x7f The population with evaluable results (n=369) excludes results missing due to progressive disease, withdrawal (including withdrawal due toOFFER YOUR1L CLL PATIENTSA CHANCE TO toxicity), deaths, unknown MRD status, and other missing samples or assessments. Not prespeci ed or tested for statistical signi cance4,5In a post hoc analysis of patients who had achieved uMRD with VEN+G, INV-assessed PFS rate 24 months after treatment completion wasLOOK FORWARD TO A TREATMENT-FREE PERIOD 92% (95% CI: 8897) compared with 56% (95% CI: 3775) in VEN+G patients with MRD positivity2,3,5**uMRD was evaluated using ASO-PCR 3 months after treatment ended and was defined as having achieved 1 CLL cell per 10,000 leukocytes.1 Assessed 3 months after treatment completion. Per the 2008 iwCLL guidelines.1,4 1L=first line; CLL=chronic lymphocytic leukemia; VEN+G=VENCLEXTA + GAZYVA; GClb=GAZYVA + chlorambucil; IRC=independent review committee; P0.0001.PFS=progression-free survival; HR=hazard ratio; CI=confidence interval. #P=0.0005.**PFS was assessed in evaluable patients who achieved uMRD in peripheral blood 3 months after treatment completion.2,3,5 MRD=minimal residual disease; INV=investigator; CR=complete remission; CRi=complete remission with incomplete hematologic recovery; ITT=intent to treat; LEARN MORE AT VENCLEXTAHCP.COMASO-PCR=allele-specific-oligonucleotide polymerase chain reaction; iwCLL=International Workshop on Chronic Lymphocytic Leukemia.Indication and Important Safety InformationIndication Neutropenia Adverse Reactions Lactation\x7f VENCLEXTA is indicated for the treatment of adult patients with chronic\x7fIn patients with CLL, Grade 3 or 4 neutropenia developed in 63% to 64%\x7f I n patients with CLL receiving combination therapy with obinutuzumab,\x7fAdvise nursing women to discontinue breastfeeding during treatmentlymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). of patients and Grade 4 neutropenia developed in 31% to 33% ofserious adverse reactions were most often due to febrile neutropenia andwith VENCLEXTA.Important Safety Information patients treated with VENCLEXTA in combination and monotherapypneumonia (5% each). The most common adverse reactions (20%) of Females and Males of Reproductive PotentialContraindication studies. Febrile neutropenia occurred in 4% to 6% of patients treated withany grade were neutropenia (60%), diarrhea (28%), and fatigue (21%). \x7fAdvise females of reproductive potential to use effective contraception \x7fConcomitant use of VENCLEXTA with strong CYP3A inhibitors at initiationVENCLEXTA in combination and monotherapy studies. \x7fIn patients with CLL receiving combination therapy with rituximab, during treatment with VENCLEXTA and for at least 30 days after the\x7f Monitor complete blood counts throughout the treatment period.the most frequent serious adverse reaction (5%) was pneumonia (9%). and during ramp-up phase is contraindicated in patients with CLL/SLLlast dose.due to the potential for increased risk of tumor lysis syndrome (TLS). Interrupt dosing or reduce dose for severe neutropenia. ConsiderThe most common adverse reactions (20%) of any grade were\x7fBased onndings in animals, male fertility may be compromised by supportive measures including antimicrobials for signs of infection andneutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), Tumor Lysis Syndrome use of growth factors (e.g., G-CSF). fatigue (22%), and nausea (21%). treatment with VENCLEXTA.\x7fTumor lysis syndrome, including fatal events and renal failure requiringInfections \x7f I n patients with CLL/SLL receiving monotherapy, the most frequentHepatic Impairmentdialysis, has occurred in patients with high tumor burden when treated\x7fFatal and serious infections such as pneumonia and sepsis have occurredserious adverse reactions (5%) were pneumonia (9%), febrile neutropenia\x7f Reduce the dose of VENCLEXTA for patients with severe hepatic with VENCLEXTA. in patients treated with VENCLEXTA. Monitor patients closely for signs (5%), and sepsis (5%). The most common adverse reactions (20%) of impairment (Child-Pugh C); monitor these patients more closely for \x7f I n patients with CLL who followed the current (5 week) dose ramp-up andand symptoms of infection and treat promptly. Withhold VENCLEXTA forany grade were neutropenia (50%), diarrhea (43%), nausea (42%), signs of toxicity. No dose adjustment is recommended for patients with the TLS prophylaxis and monitoring measures, the rate of TLS was 2% inGrade 3 and higher infection. upper respiratory tract infection (36%), anemia (33%), fatigue (32%), mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.the VENCLEXTA CLL monotherapy studies. The rate of TLS remainedImmunization thrombocytopenia (29%), musculoskeletal pain (29%), edema (22%),consistent with VENCLEXTA in combination with obinutuzumab or\x7f Do not administer live attenuated vaccines prior to, during, or afterand cough (22%).rituximab. With a 2- to 3-week dose ramp-up and higher starting dose inDrug Interactions Please see Brief Summary of full Prescribing Informationpatients with CLL/SLL, the TLS rate was 13% and included deaths andtreatment with VENCLEXTA until B-cell recovery occurs. Advise patients renal failure. that vaccinations may be less effective. \x7fConcomitant use with a P-gp inhibitor or a strong or moderate CYP3Aon the following pages.Embryo-Fetal Toxicity inhibitor increases VENCLEXTA exposure, which may increase\x7f VENCLEXTA poses a risk for TLS at initiation and during the ramp-upVENCLEXTA toxicities, including the risk of TLS. Adjust VENCLEXTA phase. Changes in blood chemistries consistent with TLS that require\x7f VENCLEXTA may cause embryo-fetal harm when administered to adosage and closely monitor patients for signs of VENCLEXTA toxicities.References: 1. VENCLEXTA Prescribing Information. 2. Data on file, AbbVie Inc. prompt management can occur as early as 6 to 8 hours following therstpregnant woman. Advise females of reproductive potential to avoidResume the VENCLEXTA dosage that was used prior to concomitant useABVRRTI69785. 3. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab dose of VENCLEXTA and at each dose increase. pregnancy during treatment. of a P-gp inhibitor or a strong or moderate CYP3A inhibitor 2 to 3 daysin patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236 \x7f Patients should be assessed for TLS risk, including evaluation of tumorIncreased Mortality in Patients with Multiple Myeloma whenafter discontinuation of the inhibitor. (suppl appendix). 4. Data on file, AbbVie Inc. ABVRRTI69608. 5. Fischer K, Al-Sawaf burden and comorbidities, and should receive appropriate prophylaxis forVENCLEXTA is Added to Bortezomib and Dexamethasone \x7fPatients should avoid grapefruit products, Seville oranges, and starfruitO, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting TLS, including hydration and anti-hyperuricemics. Reduced renal function\x7f I n a randomized trial (BELLINI; NCT02755597) in patients with relapsed orduring treatment as they contain inhibitors of CYP3A. conditions. N Engl J Med. 2019;380(23):2225-2236.further increases the risk. Monitor blood chemistries and managerefractory multiple myeloma, the addition of VENCLEXTA to bortezomib\x7f Avoid concomitant use of strong or moderate CYP3A inducers.abnormalities promptly. Interrupt dosing if needed. Employ moreplus dexamethasone, a use for which VENCLEXTA is not indicated,\x7f Avoid concomitant use of VENCLEXTA with a P-gp substrate. If intensive measures (IV hydration, frequent monitoring, hospitalization) asresulted in increased mortality. Treatment of patients with multipleconcomitant use is unavoidable, separate dosing of the P-gp substrateoverall risk increases. myeloma with VENCLEXTA in combination with bortezomib plusat least 6 hours before VENCLEXTA.\x7f Concomitant use of VENCLEXTA with P-gp inhibitors or strong ordexamethasone is not recommended outside of controlled clinical trials. \x7fMonitor international normalized ratio (INR) closely in patientsmoderate CYP3A inhibitors may increase the risk of TLS at initiation andreceiving warfarin.during the ramp-up phase, and requires dose adjustment due to increases in VENCLEXTA exposure.Distributed and marketed by AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064Marketed by Genentech USA, Inc., 1 DNA Way, South San Francisco, CA 94080-4990 VENCLEXTA is a registered trademark of AbbVie Inc.2020 AbbVie Inc. and Genentech USA, Inc. GAZYVA is a registered trademark of Genentech, Inc. US-VENC-200072/June 2020Printed in USA15_8675 US-VENC-200072.indd All Pages 7/16/20 6:47 PM'