MURANO: Final 7 year follow up and retreatment analysis in venetoclax‐rituximab (VenR)‐treated patients with relapsed/refractory chronic lymphocytic leukemia (<i>R</i>/<i>R</i> CLL)

Introduction: Fixed-duration (FD) VenR treatment (tx) in patients (pts) with R/R CLL the Phase 3 MURANO trial (NCT02005471) resulted superior progression-free survival (PFS) and overall (OS), versus bendamustine (B)R. This was sustained at 5 years (y) median (m) follow up (FU): PFS, 53.6 months [mo] 17.0 mo BR; y OS rates, 82.1% 62.2% p < 0.0001 for both. We report final analyses of 7 mFU: specifically, updated PFS OS, minimal residual disease (MRD) evaluation, pts treated main study, VenR-retreated substudy. Methods: Pts were randomized to (Ven 400 mg daily 2 + monthly R first 6 mo) or BR (6 mo). In substudy (2018 onwards), progressive (PD) received (to study regimen) as re-tx crossover from BR. investigator assessed. Peripheral blood MRD measured centrally by ASO-PCR and/or flow cytometry. Undetectable (u)MRD defined <10–4. Results: Baseline characteristics are shown Table. At data cut (3 August 2022), mPFS (95% confidence interval [CI]) VenR-treated (n = 194) 54.7 (52.3, 59.9) (15.5, 21.7) BR-treated 195; hazard ratio [HR] 0.25). Seven rates CI) 23.0% (16.1, 29.9) (no progression free this time point); 69.6% (62.8, 76.5) 51.0% (43.3, 58.7) (HR 0.53). M next tx 63.0 24.0 0.30); 37.1% have not had further anti-CLL tx. Among who uMRD end (EOT) without PD 83/118; 70.3%), EOT 52.5 (44.5, 61.5) 18.0 (8.5, 29.3; 0.0001) MRD+ 35; 29.7%). FU, 14 (16.9%) no nor confirmed conversion; 63 (75.9%) conversion, m conversion 19.4 (8.7, 28.0). converted, 39 subsequently died; 28.3 (23.2, 35.0). 34), 25 (Table), 92.0% whom ≥1 following high-risk features: IGHV-unmutated disease, genomic complexity, del(17p) TP53 mutations; despite this, 14/25 (56.0%) achieved study. Best response rate (ORR) 72.0% 23.3 (15.6, 24.3). (range) last Ven dose ramp-up 2.3 (1.2–3.1). Eight (32.0%) combination tx, but retained EOT. No new safety findings observed. Conclusions: benefits associated prolonged PFS. high risk pts, ORR attainable. These support FD CLL, suggest that is a viable option pre-treated pts. Encore Abstract - previously submitted EHA 2023 The research funded by: sponsored F. Hoffmann-La Roche Ltd AbbVie, Inc. Third-party medical writing editorial assistance, under direction authors provided Roisin Weaver, MSc, Alex Maksymowych, Ashfield MedComms, an Inizio company, Ltd. would also like thank Jenny Qun Wu, Genentech Inc, Anne-Marie van der Kevie-Kersemaekers, Amsterdam University Medical Centers, their contributions Keywords: Chronic Lymphocytic Leukemia (CLL), Combination Therapies Conflicts interests pertinent abstract A. P. Kater Employment leadership position: Consultant advisory role: Abbvie, AstraZeneca, BMS, Janssen, Genmab, LAVA, Roche/Genentech Research funding: Educational grants: Other remuneration: Leadership- HOVON: President executive board, chairman working group; UMC: Chairman Good Practice committee; EHA: Scientific Working group on CLL; ERIC: member board; Speaker’s Bureau Janssen R. Harrup AstraZeneca 20 July 2021 T. J. Kipps Ascerta/AstraZeneca; Celgene; Genentech/Roche; Gilead; Janssen; Loxo Oncology; TG Therapeutics; Verastem; Pharmacyclics/AbbVie; Breast Cancer Foundation; Md Anderson Center; Oncternal Therapeutics, Inc.; Specialized Center [SCOR] Lymphoma Society [LLS]; California Institute Regenerative Medicine [CIRM]; National Institute/NIH; VelosBio, – Agreement Honoraria: Pharmacyclics/AbbVie, Genentech/Roche, Gilead, Institute/NIH, Celgene, European Initiative [ERIC], Dava Oncology, Foundation, iwNHL, NCCN CLL/SLL Hairy Cell Panel Meeting, OncLive Patents, royalties other intellectual property Cirmtuzumab developed TJK laboratory licensed Inc., which stock options funding B. Eichhorst Hospital Cologne, Faculty Medicine; Ended employment past 24 BeiGene, MSD, Lilly Roche, MSD BeiGene Leadership Director Prof. Michael Hallek; C. Owen Merck, Incyte, Novartis, Seattle Genetics, S. Assouline Paladin, Pfizer, Novartis N. Lamanna Eli Lilly/Loxo, Genentech, Pharmacyclics MingSight, Octapharma, Oncternal, Therapeutics Robak Lodz, Copernicus Memorial Hospital, Poland Regeneron, Octapharma U. Jaeger G. Cartron Mabqi, MedxCell Gilead Sciences, M. Montillo Haematology Mellink Cytogeneticist, Human AUMC Financing array-analysis Murano sample Chyla AbbVie Stock ownership: Thadani-Mulero Lefebure Y. Jiang Roche/GNE Millen Roche; months- Hubrecht Oncode Boyer Seymour Genor Bio, Bureau- royalties, property- AbbVie; Expert testimony-