b'57FOR ELIGIBLE VETERANSIndicationVENCLEXTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).The National Comprehensive Cancer Network (NCCN) recommends venetoclax (VENCLEXTA) + obinutuzumab (GAZYVA) as a preferred 1L treatment option for patients with CLL/SLL (category 1 for patients without del(17p)/TP53 mutation who are age 65 years or age 65 years with signi cant comorbidities (creatinine clearance [CrCl] 70 mL/min)VENCLEXTAGAZYVA3Veterans exposed to Agent Orange during service are at risk for CLL.(venetoclax tablets) (obinutuzumab) 4CLL is almost twice as common in men as in women.The VENCLEXTA + GAZYVA regimen (VEN+G) is designed to be completed after 12 months (twelve 28-day treatment cycles): GAZYVA is administered in Cycles 16 and VENCLEXTA is taken orally 400 mg/day from Cycle 3, Day 1, after therst 2 cycles2 Veterans are at risk for: of GAZYVA and the 5-week VENCLEXTA dose ramp-up.COMPLICATIONS RELATED TO CLL 5 MALIGNANCIES 6 MORE FREQUENT HOSPITAL STAYS 7Such as major hemorrhage, which may be dueDiagnosed secondary to CLL 21% of VA veterans reported 1 or more hospital SUPPORT VETERANS WITH PREVIOUSLY UNTREATED CLL to use of anticoagulants or antiplatelet agents admissions per year compared with 7% of the WITH A CHEMO-FREE TREATMENT OPTION general populationDESIGNED TO STOP AFTER 12 MONTHS. 2For appropriate veterans with CLL, consider VEN+G for CLL NCCN is a trademark owned by the National Comprehensive Cancer Network (NCCN). NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibilityas a 1L treatment option. 2for their application or use in any way. *See NCCN Guidelines for the NCCN de nitions of Categories of Preference and Categories of Evidence and Consensus. 1L= rst line; CLL=chronic lymphocytic leukemia; SLL=small lymphocytic lymphoma; VA=Veterans Affairs.LEARN MORE AT VENCLEXTAHCP.COMImportant Safety Information Neutropenia Adverse Reactions Avoid concomitant use of strong or moderate CYP3A inducers.Contraindication In patients with CLL, Grade 3 or 4 neutropenia developed in 63% to 64% ofIn patients with CLL receiving combination therapy with obinutuzumab,Monitor international normalized ratio (INR) more frequently in patients receivingConcomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation andpatients and Grade 4 neutropenia developed in 31% to 33% of patients whenserious adverse reactions were most often due to febrile neutropenia andwarfarin.during ramp-up phase is contraindicated in patients with CLL/SLL due to thetreated with VENCLEXTA in combination and monotherapy studies. Febrilepneumonia (5% each). The most common adverse reactions (20%) of anyAvoid concomitant use of VENCLEXTA with a P-gp substrate. If concomitant use potential for increased risk of tumor lysis syndrome (TLS). neutropenia occurred in 4% to 6% of patients. grade were neutropenia (60%), diarrhea (28%), and fatigue (21%). Fatal adverseis unavoidable, separate dosing of the P-gp substrate at least 6 hours before Tumor Lysis SyndromeMonitor complete blood counts. Interrupt dosing for severe neutropenia andreactions that occurred in the absence of disease progression and with onsetVENCLEXTA. Tumor lysis syndrome, including fatal events and renal failure requiring dialysis,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,Lactationhas occurred in patients treated with VENCLEXTA. antimicrobials and growth factors (e.g., G-CSF). most often from infection.Advise women not to breastfeed during treatment with VENCLEXTA and for 1 week VENCLEXTA can cause rapid reduction in tumor and thus poses a risk for TLS atInfections In patients with CLL receiving combination therapy with rituximab, the mostafter the last dose.initiation and during the ramp-up phase in all patients, and during reinitiation F atal and serious infections such as pneumonia and sepsis have occurred infrequent serious adverse reaction (5%) was pneumonia (9%). The most commonFemales and Males of Reproductive Potentialafter dosage interruption in patients with CLL/SLL. Changes in blood chemistriespatients treated with VENCLEXTA. Monitor patients for signs and symptoms ofadverse reactions (20%) of any grade were neutropenia (65%), diarrhea (40%),Advise females of reproductive potential to use effective contraception during consistent with TLS that require prompt management can occur as early as 6 toinfection and treat promptly. Withhold VENCLEXTA for Grade 3 and 4 infectionupper respiratory tract infection (39%), fatigue (22%), and nausea (21%). Fataltreatment with VENCLEXTA and for 30 days after the last dose.8 hours following therst dose of VENCLEXTA and at each dose increase. TLS,until resolution and resume at same or reduced dose. adverse reactions that occurred in the absence of disease progression and within Based onndings in animals, VENCLEXTA may impair male fertility.including fatal cases, has been reported after a single 20 mg dose. Immunization 30 days of the last VENCLEXTA treatment and/or 90 days of the last rituximab wereHepatic ImpairmentIn patients with CLL/SLL who followed the current (5 week) dose ramp-up and Do not administer live attenuated vaccines prior to, during, or after treatment withreported in 2% (4/194) of patients. Reduce the dose of VENCLEXTA for patients with severe hepatic impairment the TLS prophylaxis and monitoring measures, the rate of TLS was 2% in theVENCLEXTA until B-cell recovery occurs. Advise patients that vaccinations may beIn patients with CLL/SLL receiving monotherapy, the most frequent serious(Child-Pugh C); monitor these patients more frequently for adverse reactions. VENCLEXTA CLL/SLL monotherapy trials. The rate of TLS remained consistent withless effective. adverse reactions (5%) were pneumonia (9%), febrile neutropenia (5%), andNo dose adjustment is recommended for patients with mild (Child-Pugh A) or VENCLEXTA in combination with obinutuzumab or rituximab. With a 2- to 3-weekEmbryo-Fetal Toxicity sepsis (5%). The most common adverse reactions (20%) of any grade weremoderate (Child-Pugh B) hepatic impairment.dose ramp-up and higher starting dose in patients with CLL/SLL, the TLS rate wasVENCLEXTA may cause embryo-fetal harm when administered to a pregnantneutropenia (50%), diarrhea (43%), nausea (42%), upper respiratory tract infection 13% and included deaths and renal failure. woman. Advise females of reproductive potential to use effective contraception(36%), anemia (33%), fatigue (32%), thrombocytopenia (29%), musculoskeletalPlease see Brief Summary of full Prescribing Information on the The risk of TLS is a continuum based on multiple factors, particularly reduced renalduring treatment and for 30 days after the last dose. pain (29%), edema (22%), and cough (22%). Fatal adverse reactions that occurredfollowing pages.function, tumor burden, and type of malignancy. Splenomegaly may also increaseIncreased Mortality in Patients with Multiple Myeloma when VENCLEXTA isin the absence of disease progression and within 30 days of venetoclax treatmentReferences: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in the risk of TLS in patients with CLL/SLL. Added to Bortezomib and Dexamethasone were reported in 2% of patients in the VENCLEXTA monotherapy studies, mostOncology (NCCN Guidelines) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.Assess all patients for risk and provide appropriate prophylaxis for TLS, includingIn a randomized trial (BELLINI; NCT02755597) in patients with relapsed oroften (2 patients) from septic shock. V1.2022. National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed October hydration and anti-hyperuricemics. Monitor blood chemistries and managerefractory multiple myeloma, the addition of VENCLEXTA to bortezomib plusDrug Interactions 26, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. abnormalities promptly. Employ more intensive measures (IV hydration, frequentdexamethasone, a use for which VENCLEXTA is not indicated, resulted in increasedConcomitant use with a P-gp inhibitor or a strong or moderate CYP3A inhibitor2. VENCLEXTA Prescribing Information. 3. Committee to Review the Health Effects in Vietnam monitoring, hospitalization) as overall risk increases. Interrupt dosing if needed;mortality. Treatment of patients with multiple myeloma with VENCLEXTA inincreases VENCLEXTA exposure, which may increase VENCLEXTA toxicities, includingVeterans of Exposure to Herbicides (Eleventh Biennial Update); Board on Population Health and Public Health Practice; Health and Medicine Division; National Academies of Sciences, when restarting VENCLEXTA follow dose modi cation guidance in the Prescribingcombination with bortezomib plus dexamethasone is not recommended outsidethe risk of TLS. Consider alternative medications or adjust VENCLEXTA dosage andEngineering, and Medicine. Veterans and Agent Orange: Update 11 (2018). The National Information. of controlled clinical trials. monitor more frequently for adverse reactions. Resume the VENCLEXTA dosage thatAcademies Press; 2018. 4. SEER cancer stat facts: Leukemiachronic lymphocytic leukemia (CLL).Concomitant use of VENCLEXTA with P-gp inhibitors or strong or moderate CYP3Awas used prior to concomitant use of a P-gp inhibitor or a strong or moderate CYP3ANational Cancer Institute. Accessed October 26, 2021. https://seer.cancer.gov/statfacts/html/clyl.html inhibitors increases venetoclax exposure, which may increase the risk of TLS atinhibitor 2 to 3 days after discontinuation of the inhibitor. 5. Georgantopoulos P, et al. Cancer Med. 2019;8(5):2233-2240. 6. Kyasa MJ, et al. Leuk initiation and during the ramp-up phase, and requires VENCLEXTA dose reduction.P atients should avoid grapefruit products, Seville oranges, and starfruit duringLymphoma. 2004;45(3):507-513. 7. Agha Z, et al. Arch Intern Med. 2000;160(21):3252-3257.treatment as they contain inhibitors of CYP3A.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 and its design are registered trademarks of AbbVie Inc.2021 AbbVie Inc. and Genentech USA, Inc. GAZYVA is a registered trademark of Genentech, Inc. US-VENC-210309/November 2021 Printed in USA16-5085 US-VENC-210309 AD.indd 1-2 11/29/21 3:44 PM'