b'WHAT COULD THE CHANCE FOR A Withxed-duration VENCLEXTA regimens, offer your PROGRESSION-FREE AND TREATMENT-FREE PERIOD patients the power to stop treatment and the chance for: VENCLEXTA-based regimens give patients a target MEAN FOR YOUR PATIENTS WITH CLL/SLL? treatment completion date1A TARGET STOP DATEA dened end to treatment that encourages compliance and optimizes clinical outcomes2,3 No additional VENCLEXTA regimen exposure after Indication LIMITED TIME ON TREATMENTcompleting treatment1 VENCLEXTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). A TREATMENT-FREE PERIODFixed duration offers patients a return to life without a daily VEN+G regimen: Designed to be completed after 12 monthsCLL14 trial design and primary endpoint: In a randomized clinical reminder of their treatment and disease(twelve 28-day treatment cycles): GAZYVA (obinutuzumab)trial of 432 patients (VEN+G: N=216; GClb: N=216) with previously is administered in Cycles 16, and VENCLEXTA is taken orallyuntreated CLL and with a median follow-up of 28 months (range:No additional VENCLEXTA regimen patient out-of-pocket costs 400 mg/day from Cycle 3, Day 1, after therst two cycles of036 months), VEN+G reduced the risk of progression or death by FIXED TREATMENT, FIXED COST GAZYVA and the 5-week VENCLEXTA dose ramp-up1 67% vs GClb (HR=0.33; 95% CI: 0.220.51 [P0.0001]). Median PFS after completing treatment per the recommended dosing*was not reached in either arm 1VEN+R regimen: Designed to be completed after 24 months MURANO trial design and primary endpoint: In a randomized (twenty-four 28-day treatment cycles after the 5-weekclinical trial of 389 patients (VEN+R: N=194; BR: N=195) with* Coverage and patient out-of-pocket costs for VEN+G and VEN+R vary by health plan. Patients may still incur out-of-pocket VENCLEXTA dose ramp-up): rituximab is administered inpreviously treated CLL and with a median follow-up of 23.4 months costs for other treatments or tests as directed by their healthcare providers.Cycles 16; VENCLEXTA is taken orally 400 mg/day from (range: 037.4+ months), VEN+R reduced the risk of progression orCycle 1, Day 1 of rituximab through Cycle 241 death by 81% vs BR (HR=0.19; 95% CI: 0.130.28 [P0.0001]). MedianPFS not reached in VEN+R vs 18.1 months in BR (95% CI: 15.822.3) 1VEN+G=VENCLEXTA + GAZYVA; VEN+R=VENCLEXTA + rituximab; GClb=GAZYVA + chlorambucil; HR=hazard ratio; CI=con dence interval;PFS=progression-free survival; BR=bendamustine + rituximab; 1L= rst line; R/R=relapsed/refractory. To learn more, scan the code or visit VENCLEXTAHCP.COM/CLLExplore over 5 years of follow-up data for VENCLEXTA in both 1L and R/R CLLImportant Safety InformationContraindication Neutropenia Adverse Reactions Patients should avoid grapefruit products, Seville oranges, and starfruit during Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and I n patients with CLL, Grade 3 or 4 neutropenia developed in 63% to 64% of In patients with CLL receiving combination therapy with obinutuzumab, treatment as they contain inhibitors of CYP3A.during ramp-up phase is contraindicated in patients with CLL/SLL due to thepatients and Grade 4 neutropenia developed in 31% to 33% of patients whenserious adverse reactions were most often due to febrile neutropenia andAvoid concomitant use of strong or moderate CYP3A inducers. potential for increased risk of tumor lysis syndrome (TLS). treated with VENCLEXTA in combination and monotherapy studies. Febrilepneumonia (5% each). The most common adverse reactions (20%) of any Monitor international normalized ratio (INR) more frequently in patientsTumor Lysis Syndrome neutropenia occurred in 4% to 6% of patients. grade were neutropenia (60%), diarrhea (28%), and fatigue (21%). Fatal adversereceiving warfarin.Tumor lysis syndrome, including fatal events and renal failure requiring dialysis, Monitor complete blood counts. Interrupt dosing for severe neutropenia andreactions that occurred in the absence of disease progression and with onsetAvoid concomitant use of VENCLEXTA with a P-gp substrate. If concomitant use has occurred in patients treated with VENCLEXTA. resume at same or reduced dose. Consider supportive measures includingwithin 28 days of the last study treatment were reported in 2% (4/212) of patients,is unavoidable, separate dosing of the P-gp substrate at least 6 hours before VENCLEXTA can cause rapid reduction in tumor and thus poses a risk for TLS atantimicrobials and growth factors (e.g., G-CSF). most often from infection. VENCLEXTA.initiation and during the ramp-up phase in all patients, and during reinitiationInfections In patients with CLL receiving combination therapy with rituximab, the mostLactationafter dosage interruption in patients with CLL/SLL. Changes in blood chemistriesFatal and serious infections such as pneumonia and sepsis have occurred infrequent serious adverse reaction (5%) was pneumonia (9%). The most common Advise women not to breastfeed during treatment with VENCLEXTA and for 1 week consistent with TLS that require prompt management can occur as early as 6 topatients treated with VENCLEXTA. Monitor patients for signs and symptoms ofadverse reactions (20%) of any grade were neutropenia (65%), diarrhea (40%),after the last dose.8 hours following therst dose of VENCLEXTA and at each dose increase. TLS,infection and treat promptly. Withhold VENCLEXTA for Grade 3 and 4 infectionupper respiratory tract infection (39%), fatigue (22%), and nausea (21%). FatalFemales and Males of Reproductive Potentialincluding fatal cases, has been reported after a single 20 mg dose. until resolution and resume at same or reduced dose. adverse reactions that occurred in the absence of disease progression and withinAdvise females of reproductive potential to use effective contraception during In patients with CLL/SLL who followed the current (5 week) dose ramp-up andImmunization 30 days of the last VENCLEXTA treatment and/or 90 days of the last rituximab weretreatment with VENCLEXTA and for 30 days after the last dose.the TLS prophylaxis and monitoring measures, the rate of TLS was 2% in the Do not administer live attenuated vaccines prior to, during, or after treatment withreported in 2% (4/194) of patients.Based onndings in animals, VENCLEXTA may impair male fertility.VENCLEXTA CLL/SLL monotherapy trials. The rate of TLS remained consistent withVENCLEXTA until B-cell recovery occurs. Advise patients that vaccinations may beIn patients with CLL/SLL receiving monotherapy, the most frequent seriousHepatic ImpairmentVENCLEXTA in combination with obinutuzumab or rituximab. With a 2- to 3-weekless effective. adverse reactions (5%) were pneumonia (9%), febrile neutropenia (5%), andReduce the dose of VENCLEXTA for patients with severe hepatic impairmentdose ramp-up and higher starting dose in patients with CLL/SLL, the TLS rate wassepsis (5%). The most common adverse reactions (20%) of any grade were 13% and included deaths and renal failure. Embryo-Fetal Toxicity neutropenia (50%), diarrhea (43%), nausea (42%), upper respiratory tract infection(Child-Pugh C); monitor these patients more frequently for adverse reactions.The risk of TLS is a continuum based on multiple factors, particularly reduced renal VENCLEXTA may cause embryo-fetal harm when administered to a pregnant(36%), anemia (33%), fatigue (32%), thrombocytopenia (29%), musculoskeletalNo dose adjustment is recommended for patients with mild (Child-Pugh A) orfunction, tumor burden, and type of malignancy. Splenomegaly may also increase woman. Advise females of reproductive potential to use effective contraceptionpain (29%), edema (22%), and cough (22%). Fatal adverse reactions that occurredmoderate (Child-Pugh B) hepatic impairment.the risk of TLS in patients with CLL/SLL. during treatment and for 30 days after the last dose. in the absence of disease progression and within 30 days of venetoclax treatmentAssess all patients for risk and provide appropriate prophylaxis for TLS, includingIncreased Mortality in Patients with Multiple Myeloma whenwere reported in 2% of patients in the VENCLEXTA monotherapy studies, mostPlease see Brief Summary of full Prescribing Information on thehydration and anti-hyperuricemics. Monitor blood chemistries and manageVENCLEXTA is Added to Bortezomib and Dexamethasone often (2 patients) from septic shock. following pages.abnormalities promptly. Employ more intensive measures (IV hydration, frequent I n a randomized trial (BELLINI; NCT02755597) in patients with relapsed orDrug Interactions References: 1. VENCLEXTA Prescribing Information. 2. Greer JA, Amoyal N, Nisotel L, et al. A monitoring, hospitalization) as overall risk increases. Interrupt dosing if needed;refractory multiple myeloma, the addition of VENCLEXTA to bortezomib plus Concomitant use with a P-gp inhibitor or a strong or moderate CYP3A inhibitorsystematic review of adherence to oral antineoplastic therapies.Oncologist. 2016;21(3):354-when restarting VENCLEXTA follow dose modi cation guidance in the Prescribingdexamethasone, a use for which VENCLEXTA is not indicated, resulted in increasedincreases VENCLEXTA exposure, which may increase VENCLEXTA toxicities, including376. 3. Ruddy K, Mayer E, Partridge A. Patient adherence and persistence with oral anticancer Information. mortality. Treatment of patients with multiple myeloma with VENCLEXTA inthe risk of TLS. Consider alternative medications or adjust VENCLEXTA dosage andtreatment. CA Cancer J Clin. 2009;59(1):56-66.Concomitant use of VENCLEXTA with P-gp inhibitors or strong or moderate CYP3Acombination with bortezomib plus dexamethasone is not recommended outsidemonitor more frequently for adverse reactions. Resume the VENCLEXTA dosage that inhibitors increases venetoclax exposure, which may increase the risk of TLS atof controlled clinical trials. was used prior to concomitant use of a P-gp inhibitor or a strong or moderate CYP3A initiation and during the ramp-up phase, and requires VENCLEXTA dose reduction. inhibitor 2 to 3 days after discontinuation of the inhibitor.VENCLEXTA and its design are registered trademarks of AbbVie Inc.2022 AbbVie and Genentech USA, Inc. All rights reserved. GAZYVA and its design are registered trademarks of Genentech, Inc. US-VENC-220137/August 202216_8206 US-VENC-220137.indd All Pages 8/16/22 3:10 PM'