b'WHAT COULD THE CHANCE FOR A Withxed-duration VENCLEXTA regimens, offer your patients the power to stop treatment and the chance for:adults in the U.S. can access the vaccine as quickly PROGRESSION-FREE AND TREATMENT-FREE PERIOD as possible and to progress regulatory review in oth-er countries, said Tony Wood, chief scientific officeVENCLEXTA-based regimens give patients a target MEAN FOR YOUR PATIENTS WITH CLL/SLL? of GSK, which is launching the vaccine. treatment completion date1A TARGET STOP DATEA dened end to treatment that encourages compliance and In the study that led to FDA approval, the vaccine was shown to significantly reduce the risk of devel-optimizes clinical outcomes2,3oping RSV-associated lower respiratory tract diseaseNo additional VENCLEXTA regimen exposure after Indication LIMITED TIME ON TREATMENT (LRTD) by 82.6% and reduced the risk of develop- completing treatment1ing severe RSV-associated LRTD by 94.1%.VENCLEXTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). AnFDAadvisorypanelrecentlyrecommended 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 thatArexvyandanothercandidatefromPfizerbe 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 previouslyapproved to protect against RSV in older adults. is administered in Cycles 16, and VENCLEXTA is taken orallyuntreated CLL and with a median follow-up of 28 months (range: The FDA has said that RSV contributes to more 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 No additional VENCLEXTA regimen patient out-of-pocket costs after completing treatment per the recommended dosing*GAZYVA and the 5-week VENCLEXTA dose ramp-up1 67% vs GClb (HR=0.33; 95% CI: 0.220.51 [P0.0001]). Median PFS than 10,000 deaths a year among people over age 65, was not reached in either arm 1 plus at least 60,000 hospitalizations. Electron micrograph of RSV VEN+R regimen: Designed to be completed after 24 monthsMURANO trial design and primary endpoint: In a randomizedAnotherrecentindustrystudy,publishedinclinical 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(twenty-four 28-day treatment cycles after the 5-weekClinicalInfectiousDiseases,modeledtheepide- of RSV-coded hospitalizations within VA (exclud-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.(range: 037.4+ months), VEN+R reduced the risk of progression or miology of RSV in the United States, with a spe- ing all non-VA hospitalizations) had a documented Cycles 16; VENCLEXTA is taken orally 400 mg/day fromCycle 1, Day 1 of rituximab through Cycle 241 death by 81% vs BR (HR=0.19; 95% CI: 0.130.28 [P0.0001]). Median cial focus on adults 60 and older with and withoutpositive test result.PFS not reached in VEN+R vs 18.1 months in BR (95% CI: 15.822.3) 1 vaccination. 3 The study found a greater than 15-fold increase in Intheabsenceofavaccine,weproject17.5- RSV tests performed, although the percent testing VEN+G=VENCLEXTA + GAZYVA; VEN+R=VENCLEXTA + rituximab; GClb=GAZYVA + chlorambucil; HR=hazard ratio; CI=con dence interval; 22.6 million symptomatic RSV ARI cases per yearpositive remained relatively stable PFS=progression-free survival; BR=bendamustine + rituximab; 1L= rst line; R/R=relapsed/refractory. To learn more, scan the code or visit VENCLEXTAHCP.COM/CLLin 18-year-olds in the U.S., with 3.6-4.8 million/ RSVtestingandidentificationofpatientswith year occurringr 5 y 60-year-olds,w- cordatto t reENCLE infectionth 1L and R/R CLL duringthe Explore ove inears of follo ac up ding a fo h V RSV XTA in bo increaseddramaticallyImportant Safety Information authors.Modelingindicatesthatupto2.0mil- time period analyzed, likely due to increased avail-lion symptomatic RSV ARI cases per year couldabilityofPCR-basedmulti-pathogenpanelsand Contraindication Neutropenia Adverse ReactionsP atients should avoid grapefruit products, Seville oranges, and starfruit during treatment as they contain inhibitors of CYP3A.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% ofbe pa reventedin60-year-oldserapy hith hypotheti , duplex assays, the Vauthors concluded. WhileIn p tients with CLL receiving combination th witw aobinutuzumab - Aduring 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 and Avoid concomitant use of strong or moderate CYP3A inducers.cal vaccine (70% vaccine efficacy against symp- the percentage of tests positive for RSV remained 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 patients grade were neutroand 60dia v ea (28%), and fatigue (21%). Fatal adversereceiving warfarin.Tumor Lysis Syndrome neutropenia occurred in 4% to 6% of patients. tomatic ARI, penia (60%), %rrh accine coverage), and uprelatively stable, the rise in coded hospitalizations 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 onset Avoid concomitant use of VENCLEXTA with a P-gp substrate. If concomitant use to 0.69 million cases per year can be prevented inmay be due to increased testing for RSV among hos-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 antimicrobials and growth factors (e.g., G-CSF). the ost often from infecti ed population, assuming 50% vac- pitalized veterans with severe respiratory infections. VENCLEXTA can cause rapid reduction in tumor and thus poses a risk for TLS atmnonvaccinat on. VENCLEXTA.initiation and during the ramp-up phase in all patients, and during reinitiationInfections cine impact on infectiousness. In adult populations,LactationIn patients with CLL receiving combination therapy with rituximab, the mostThese surveillance data may allow for further char-after 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 commonAdvise women not to breastfeed during treatment with VENCLEXTA and for 1 week diagnostictestingforRSVhashistoricallybeenacterization of RSV disease burden estimates which 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.upper respiratory tract infection (39%), fatigue (22%), and nausea (21%). FatalFemales and Male clinical management 8 hours following therst dose of VENCLEXTA and at each dose increase. TLS,infection and treat promptly. Withhold VENCLEXTA for Grade 3 and 4 infectionunderutilized. can help informs of Reproductive Potential and develop-including 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 within Advise females of reproductive potential to use effective contraception during The researchers from the Palo Alto, CA, VAMCment of interventions for adults, such as vaccines 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.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.the TLS prophylaxis and monitoring measures, the rate of TLS was 2% in theincluded 102,251 RSV results, finding that, overall,and antiviral therapies.VENCLEXTA CLL/SLL monotherapy trials. The rate of TLS remained consistent with In patients with CLL/SLL receiving monotherapy, the most frequent serious VENCLEXTA until B-cell recovery occurs. Advise patients that vaccinations may be 4,372(4.3%)specimensfrom4,263uniqueindi- 1 Hepatic ImpairmentVENCLEXTA in combination with obinutuzumab or rituximab. With a 2- to 3-weekadverse reactions (5%) were pneumonia (9%), febrile neutropenia (5%), and Lucero-Obusan C, Schirmer P, Oda G, Holodniy M. 1718. Respiratory less effective. Reduce the dose of VENCLEXTA for patients with severe hepatic impairmentdose ramp-up and higher starting dose in patients with CLL/SLL, the TLS rate wasviduals were positive with a median age of 67 yearsSyncytial Virus (RSV) Surveillance in the Department of Veterans Af-sepsis (5%). The most common adverse reactions (20%) of any grade were Embryo-Fetal Toxicity neutropenia (50%), diarrhea (43%), nausea (42%), upper respiratory tract infection(Child-Pugh C); monitor these patients more frequently for adverse reactions.13% and included deaths and renal failure. fairs (VA), 2010-2018. Open Forum Infect Dis. 2020 Dec 31;7(Suppl VENCLEXTA may cause embryo-fetal harm when administered to a pregnant(range 0-101). Most, 90%, were male.No dose adjustment is recommended for patients with mild (Child-Pugh A) orThe risk of TLS is a continuum based on multiple factors, particularly reduced renal(36%), anemia (33%), fatigue (32%), thrombocytopenia (29%), musculoskeletal1):S843. doi: 10.1093/ofid/ofaa439.1896. PMCID: PMC7778290.woman. Advise females of reproductive potential to use effective contraceptionAnother 1,511 patients (35.4%) also had an RSV rredmoderate (Child-Pugh B) hepatic impairment.function, tumor burden, and type of malignancy. Splenomegaly may also increase during treatment and for 30 days after the last dose. pain (29%), edema (22%), and cough (22%). Fatal adverse reactions that occu - 2in the absence of disease progression and within 30 days of venetoclax treatment Savic M, Penders Y, Shi T, Branche A, Piron JY. Respiratory syncytial the risk of TLS in patients with CLL/SLL. coded hospitalization, although RSV type was speci- Please see Brief Summary of full Prescribing Information on theAssess 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, mostvirus disease burden in adults aged 60 years and older in high-income hydration and anti-hyperuricemics. Monitor blood chemistries and manageVENCLEXTA is Added to Bortezomib and Dexamethasone fied for only 7.8% of positives. following pages. I n a randomized trial (BELLINI; NCT02755597) in patients with relapsed oroften (2 patients) from septic shock. countries: A systematic literature review and meta-analysis. Influenza abnormalities promptly. Employ more intensive measures (IV hydration, frequentD Duringtions therewere2,522RSV- Other Respir Viruses. 2023 Jan;17(1):e13031. doi: 10.1111/irv.13031. refractory multiple myeloma, the addition of VENCLEXTA to bortezomib plusrug Interac 2010-2018References: 1. VENCLEXTA Prescribing Information. 2. Greer JA, Amoyal N, Nisotel L, et al. A monitoring, hospitalization) as overall risk increases. Interrupt dosing if needed;Concomitant use with a P-gp inhibitor or a strong or moderate CYP3A inhibitorE sy ub 2 at 22 Nov11. PMID:363697 tineoplastic ID: rapies. Onco5463.dexamethasone, a use for which VENCLEXTA is not indicated, resulted in increasedcodedhospitalizations(medianlengthofstay=p stem 0 ic reviewof adherenceto oral an 72; PMCthePMC983logist. 2016;21(3):354-when restarting VENCLEXTA follow dose modi cation guidance in the Prescribingincreases VENCLEXTA exposure, which may increase VENCLEXTA toxicities, including376. 3. Ruddy K, Mayer E, Partridge A. Patient adherence and persistence with oral anticancer mortality. Treatment of patients with multiple myeloma with VENCLEXTA in3 treatment.C rre T, Hens N, White LJ, Gravenstein S, et. al. Modeling Information. 4days) among2,444uniqueindiv VENCLEXTA which Van Effelte A Cancer J Clin. 2009;59(1):56-66.combination with bortezomib plus dexamethasone is not recommended outsidethe risk ofTLS. Consider alternative medications or adjustiduals,dosage and Concomitant use of VENCLEXTA with P-gp inhibitors or strong or moderate CYP3Amonitor more frequently for adverse reactions. Resume the VENCLEXTA dosage thatRespiratory Syncytial Virus Adult Vaccination in the United States with of controlled clinical trials. included413ICUstays(16.4%)and98deaths inhibitors increases venetoclax exposure, which may increase the risk of TLS atwas used prior to concomitant use of a P-gp inhibitor or a strong or moderate CYP3Aa Dynamic Transmission Model. Clin Infect Dis. 2023 Mar 23:ciad161. initiation and during the ramp-up phase, and requires VENCLEXTA dose reduction. (3.9%)duringtheRSV-codedhospitalization, inhibitor 2 to 3 days after discontinuation of the inhibitor. doi: 10.1093/cid/ciad161. Epub ahead of print. PMID: 36949605.the researchers pointed out. Approximately 78% 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 202211316_8206 US-VENC-220137.indd All Pages 8/16/22 3:10 PM'