Allan, John N

Badoux, Xavier C

Barca, Eva Gonzalez

Barrientos, Jacqueline C

Flinn, Ian W

Ghia, Paolo

Jacobs, Ryan

Kipps, Thomas J

Kuss, Bryone J

Opat, Stephen

Siddiqi, Tanya

Szafer-Glusman, Edith

Szoke, Anita

Tam, Constantine S

Tedeschi, Alessandra

Wierda, William G

Zhou, Cathy

Blood

English

eScholarship - University of California

UC San DiegoUC San Diego Previously Published WorksTitleTreatment Outcomes after Undetectable MRD with First-Line Ibrutinib (Ibr) Plus Venetoclax (Ven): Fixed Duration Treatment (Placebo) Versus Continued Ibr with up to 5 Years Median Follow-up in the CAPTIVATE StudyPermalinkhttps://escholarship.org/uc/item/8b0557s9JournalBlood, 140(Supplement 1)ISSN0006-4971AuthorsAllan, John NSiddiqi, TanyaKipps, Thomas Jet al.Publication Date2022-11-15DOI10.1182/blood-2022-160338Copyright InformationThis work is made available under the terms of a Creative Commons Attribution License, available at https://creativecommons.org/licenses/by/4.0/ Peer reviewedeScholarship.org Powered by the California Digital LibraryUniversity of California224 15 NOBlood (2022) 140 (Supplement 1): 224–227VEMBER 2022 | VOLUME 140, NUMBER Supplement 1 © 2022 by The American Society o64th ASH Annual Meeting AbstractsORAL ABSTRACTS642.CHRONIC LYMPHOCYTIC LEUKEMIA: CLINICAL AND EPIDEMIOLOGICALTreatment Outcomes after Undetectable MRD with First-Line Ibrutinib (Ibr) Plus Venetoclax (Ven): Fixed DurationTreatment (Placebo) Versus Continued Ibr with up to 5 Years Median Follow-up in the CAPTIVATE StudyJohn N. Allan1, Tanya Siddiqi, MD2,*, Thomas J. Kipps, MD PhD3, Bryone J. Kuss, MBBS, PhD FRACP, FRCPA4,*,Xavier C. Badoux, MBBS, FRACP, FRCPA5, Jacqueline C. Barrientos, MD MS6,*, Alessandra Tedeschi7,*,Stephen Opat, FRACP, FRCPA, MBBS8,*, Ian W. Flinn, MDPhD9, Eva Gonzalez Barca, MD PhD10,*, Ryan Jacobs, MD11,*,Edith Szafer-Glusman, PhD12,*, Cathy Zhou, MS12,*, Anita Szoke, MD12,*, William G. Wierda, MD PhD13,*,Paolo Ghia, MDPhD14, Constantine S. Tam, MD15,*1Weill Cornell Medicine, New York, NY2City of Hope National Medical Center, Duarte,3UC San Diego Moores Cancer Center, San Diego, CA4Flinders University and Medical Center, Bedford Park, Australia5Ministry of Health, Kogarah, Australia6Mount Sinai Comprehensive Cancer Center, Miami Beach, FL7ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy8Monash University, Clayton, Australia9Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN10Universitat de Barcelona, Institut Catalá d'Oncologia Hospitalet, Barcelona, Spain11Levine Cancer Institute, Charlotte, NC12Pharmacyclics LLC, an AbbVie Company, South San Francisco, CA13Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX14Universita' Vita-Salute San Raffaele C.F. 97187560152, Milano, Italy15Peter MacCallum Cancer Centre, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia*Asterisk with author names denotes non-ASH members.Abstract Background: Ibr and Ven are oral inhibitors of BTK and BCL-2, respectively, approved as single agents or incombination with obinutuzumab for CLL treatment (tx). With distinct and complementary mechanisms of action, Ibr and Venwork synergistically to mobilize CLL cells from lymph nodes and lymphoid niches, enhance cell killing, and eliminate distinctCLL cell populations. CAPTIVATE (NCT02910583) is an international, multicenter phase 2 study evaluating first-line Ibr + Venin patients (pts) with CLL/SLL who have indication for tx. In this MRD cohort, after completion of Ibr + Ven, pts with Confirmedundetectable minimal residual disease (uMRD) were randomly assigned to placebo (PBO) (ie, a fixed-duration regimen), orcontinued Ibr. At primary analysis, disease-free survival (DFS) rates were similar in pts from these 2 arms (95% and 100%,respectively), 2 y after randomization (Ghia et al. ASH 2021). Here we present efficacy and safety results with median 56 mo(range, 25-68) follow-up (median 41 mo post randomization).Methods: Pts aged ≤70 y with previously untreated CLL received 3 cycles of Ibr lead-in then 13 cycles of combined Ibr + Ven(oral Ibr 420 mg/d; oral Ven ramp-up to 400 mg/d). Pts achieving Confirmed uMRD (uMRD serially over at least 3 cycles, inboth peripheral blood and bone marrow) with Ibr + Ven were then randomly assigned 1:1 to double-blinded tx with PBO orsingle-agent Ibr. Endpoints included investigator-assessed best response per iwCLL, rates of uMRD (<10-4 by 8-color flowcytometry), DFS rate (time from randomization to MRD relapse [for a confirmed uMRD pt, ≥10-2 CLL cells/leukocytesconfirmed on 2 serial visits], PD per investigator assessment, or death, whichever occurs first), PFS, OS, and AEs.Results: 164 pts were enrolled to receive combined Ibr + Ven tx; after completion, 86 pts with Confirmed uMRD wererandomly assigned to PBO or single-agent Ibr (n=43 each). Baseline characteristics were previously reported (Wierda et al. JClin Oncol. 2021;39:3853). For pts with Confirmed uMRD, median time on study was 56 mo (Ibr arm range, 25‒68 mo; PBOarm range, 40‒65 mo); median post-randomization follow-up was 41.2 mo and 41.5 mo in the PBO and Ibr arms, respectively.f HematologyORAL ABSTRACTS Session 642In the PBO arm, 63% of pts have now achieved a best response of CR (increased from 60% at 2 y); among pts who continuedIbr, 81% achieved a best response of CR (increased from 72% at 2 y). Rates of uMRD remained stable from y 2 to y 3 postrandomization (PBO, 56% [n=24] and 58% [n=25]; Ibr 60% [n=26] and 63% [n=27], respectively). The 3-y DFS rate was 85% (95%CI, 69‒93) with PBO and 93% (95% CI, 80‒98) among pts who continued Ibr (p=0.1621). The 4-y PFS was 88% (95% CI, 74‒95)with PBO and 95% (95% CI, 82‒99) with continued Ibr; 4-y OS was 100% (n=0 deaths) and 98% (95% CI, 84‒100), respectively.Notably, efficacy outcomes in high-risk subgroups were consistent with the total population although low sample size in thePBO arm limits interpretation (Table). Prevalence of AEs during the post-randomization period was generally stable in eacharm (Table). New occurrences of hypertension in post randomization ys 1-3 were generally lower with PBO vs Ibr (y 1, n=1/43vs n=3/43; y 2, n=1/41 vs n=4/41; y 3, n=3/38 vs n=2/41, respectively). No new atrial fibrillation or grade ≥3 hemorrhage eventsoccurred in the PBO arm during the 3-y post randomization period; 1 pt in the Ibr arm had atrial fibrillation in 2nd y postrandomization. In the 3rd y post randomization, no pts had dose reduction or discontinuation due to an AE as expected in thePBO arm; 1/41 pts had a dose reduction and 2/41 discontinued Ibr due to an AE. In total, 7 and 2 pts have experiencedprogressive disease in the PBO and Ibr arms, respectively; 4/7 pts in the PBO arm have initiated subsequent therapy (3 withIbr, 1 with other agent/s; 0 pts in the Ibr arm have initiated subsequent tx).Conclusions: First-line Ibr + Ven is an all-oral, once-daily, chemotherapy-free regimen that continues to provide deep,durable clinical responses in pts with CLL. With an additional y of follow-up in pts with Confirmed uMRD after Ibr + Ven, 4-yOS rates were ≥98% and 4-y PFS rates were ≥88% in pts randomly assigned to PBO (representing fixed duration) or continuedIbr. The durability of uMRD and the 3-y DFS rate of 85% without ongoing tx are encouraging and support the promisingpotential for tx-free remission. Together with the safety data, these results demonstrate a favorable benefit-risk profile withfixed duration Ibr + Ven.Figure 1.ABSTRACTS 15 NOVEMBER 2022 | VOLUME 140, NUMBER Supplement 1 225ORAL ABSTRACTS Session 642Disclosures Allan: Genentech: Consultancy, Research Funding; PCYC: Consultancy, Speakers Bureau; BeiGene: Consul-tancy, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Epizyme: Consultancy; ADC Therapeutics: Con-sultancy; Ascentage: Consultancy; Celgene: Research Funding; Janssen: Honoraria, Research Funding, Speakers Bureau;AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, SpeakersBureau. Siddiqi: Beigene: Consultancy, Research Funding, Speakers Bureau; Astrazeneca: Consultancy, Research Funding,Speakers Bureau; Ascentage Pharm: Research Funding; Oncternal: Research Funding; TG Therapeutics: Research Funding;Kite Pharma: Consultancy, Research Funding; BMS: Consultancy; Celgene: Consultancy; Juno Therapeutics: Consultancy,Research Funding; Jannsen: Speakers Bureau; Pharmacyclics: Research Funding, Speakers Bureau. Kipps: Pharmacyclics, LLCan AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Genentech-Roch: Consul-tancy, Research Funding; Oncternal: Research Funding; Gilead: Consultancy; Celgene: Consultancy. Kuss: Mundipharma:Consultancy, Honoraria; Roche Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Commonwealth Serum Labora-tories: Current equity holder in private company, Current holder of stock options in a privately-held company; AbbVie:Consultancy, Honoraria, Other: expert textinomy, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau;Merck: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Kyowa Kirin: Consultancy, Honoraria. Badoux: AbbVie:Honoraria, Other: travel, accomodations, expenses; Janssen: Honoraria. Barrientos: Janssen: Honoraria; Beigene: Consul-tancy; AbbVie: Consultancy; AstraZeneca: Consultancy; MEI: Consultancy; Oncternal: Research Funding; Velosbio: ResearchFunding; Pharmacyclics, LLC an AbbVie Company: Research Funding. Tedeschi: Beigene: Consultancy, Honoraria, Other:Travel, Accommodations, Expenses, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Travel, Accommodations,Expenses, Speakers Bureau; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau;AstraZeneca: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau. Opat: Pharmacyclics,LLC an AbbVie Company: Research Funding; Antegene: Consultancy, Honoraria, Research Funding; CSL: Consultancy,Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria,Research Funding; Merck: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding;Roche: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy,Honoraria, Research Funding; Belgene: Research Funding. Flinn: Genentech: Consultancy, Research Funding; Kite Pharma:Consultancy, Research Funding; Seattle Genetics: Research Funding; Trillium Therapeutics: Research Funding; Genmab:Consultancy; Curis: Research Funding; Forma Therapeutics: Research Funding; Forty Seven: Research Funding; IGM Bio-sciences: Research Funding; Incyte: Research Funding; Celgene: Research Funding; Constellation Pharmaceuticals: ResearchFunding; Acerta Pharma: Research Funding; Agios: Research Funding; ArQule: Research Funding; Gilead Sciences: ResearchFunding; Hutchison MediPharma: Consultancy; Fate Therapeutics: Research Funding; Infinity Pharmaceuticals: ResearchFunding; Loxo@Lilly: Research Funding; Bristol Myers Squibb: Research Funding; Biopath: Research Funding; CALIBR:Research Funding; CALGB: Research Funding; Iksuda Therapeutics: Consultancy; Nurix Therapeutics: Consultancy, ResearchFunding; InnoCare Pharma: Consultancy, Research Funding; Vincerx Pharma: Consultancy, Membership on an entity's Boardof Directors or advisory committees; TG Therapeutics: Consultancy, Research Funding; Unum Therapeutics: ResearchFunding; Verastem: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Epizyme: Research Fund-ing; Novartis: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Tessa Therapeutics: ResearchFunding; Merck: Research Funding; Xencor: Consultancy; Myeloid Therapeutics: Research Funding; Portola Pharmaceuticals:Research Funding; Secura Bio: Consultancy; Rhizen Pharmaceuticals: Research Funding; Roche: Consultancy, ResearchFunding; Takeda: Consultancy; Servier Pharmaceuticals: Consultancy; Pharmacyclics: Consultancy, Research Funding; Bei-Gene: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Fund-ing; Century Therapeutics: Consultancy; Pfizer: Research Funding; CTI Biopharma: Research Funding; City of Hope NationalMedical Center: Research Funding; Millenium Pharmaceuticals: Research Funding; TCR2 Therapeutics: Research Funding;2seventy bio: Research Funding; Triphase Research & Development Corp: Research Funding. Gonzalez Barca: Takeda:Honoraria; Incyte: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; EUSA Pharma: Honoraria, Other: travel,accommodations, expenses; Roche: Honoraria; Janssen: Consultancy, Honoraria, Other: travel, accommodations, expenses;Novartis: Consultancy; Beigene: Consultancy; Gilead: Consultancy; Kiowa: Consultancy; Lilly: Consultancy. Jacobs: TGTherapeutics: Research Funding; Janssen: Speakers Bureau; Beigene: Speakers Bureau; Teneobio: Research Funding;Verastem: Consultancy; MEI Pharma: Research Funding; AstraZeneca: Consultancy, Speakers Bureau; Pharmacyclics, anAbbAvie Company: Consultancy, Research Funding, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau. Szafer-Glusman: AbbVie: Current Employment, Current equity holder in private company, Current holder of stock options in aprivately-held company. Zhou: AbbVie: Current Employment, Current equity holder in private company, Current holder ofstock options in a privately-held company. Szoke: Pharmacyclics, an AbbVie Company: Current Employment; AbbVie: Cur-rent equity holder in private company, Current holder of stock options in a privately-held company. Wierda: GSK/Novartis:Research Funding; AbbVie: Research Funding; Oncternal Therapeutics: Research Funding; Miragen: Research Funding; KitePharma: Research Funding; Bristol Myers Squibb (June and Celgene): Research Funding; Cyclacel: Research Funding;Sunesis: Research Funding; Loxo Oncology/Lilly: Research Funding; Gilead Sciences: Research Funding; AstraZeneca/AcertaPharma: Research Funding; Pharmacyclics, LLC an AbbVie Company: Research Funding; Janssen: Research Funding; Xencor:Research Funding; Genentech: Research Funding. Ghia: Lilly/Loxo: Consultancy, Honoraria; MSD: Consultancy, Honoraria;226 15 NOVEMBER 2022 | VOLUME 140, NUMBER Supplement 1 ABSTRACTSORAL ABSTRACTS Session 642Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria; BMS:Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, ResearchFunding. Tam: LOXO: Honoraria; AbbVie: Honoraria, Research Funding; Beigene: Honoraria, Research Funding; AstraZeneca:Honoraria; Janssen: Honoraria, Research Funding.OffLabel Disclosure: Ibrutinib in combination with venetoclax is not approved in any indication.https://doi.org/10.1182/blood-2022-160338ABSTRACTS 15 NOVEMBER 2022 | VOLUME 140, NUMBER Supplement 1 227

Treatment Outcomes after Undetectable MRD with First-Line Ibrutinib (Ibr) Plus Venetoclax (Ven): Fixed Duration Treatment (Placebo) Versus Continued Ibr with up to 5 Years Median Follow-up in the CAPTIVATE Study

John N. Allan

Tanya Siddiqi

Thomas J. Kipps

Bryone J. Kuss

Xavier C. Badoux

Jacqueline C. Barrientos

Alessandra Tedeschi

Stephen Opat

Ian W. Flinn

Eva Gonzalez Barca

Ryan Jacobs

Edith Szafer-Glusman

Cathy Zhou

Anita Szoke

William G. Wierda

Paolo Ghia

Constantine S. Tam

Crossref

https://ashpublications.org/blood/article/140/Supplement%201/224/488680/Treatment-Outcomes-after-Undetectable-MRD-with

Treatment Outcomes after Undetectable MRD with First-Line Ibrutinib (Ibr) Plus Venetoclax (Ven): Fixed Duration Treatment (Placebo) Versus Continued Ibr with up to 5 Years Median Follow-up in the CAPTIVATE Study

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