Multicenter Phase II Trial of Zanubrutinib, Obinutuzumab, and Venetoclax (BOVen) in Treatment-Naïve Chronic Lymphocytic Leukemia: 5-Year Follow up, Retreatment Outcomes, and Impact of MRD Kinetics (ΔMRD400)

作者：Jacob D. Soumerai, Ahmet Doǧan, Venkatraman Seshan, K. T. Flaherty, Natalie Slupe, Jason Carter, Ephraim P. Hochberg, Jeffrey A. Barnes, Jeremy S. Abramson, Audrey Hamilton, Ariela Noy, Colette Owens, Maria Lia Palomba, Anita Kumar, Lindsey E. Roeker, Meghan C. Thompson, Ronald W. Takvorian, Zachary D. Epstein‐Peterson, Mark B. Geyer, Gilles Salles, Robert Stuver, Philip Caron, Prioty Islam, Tamanna Haque, Paola Ghione, Raphaël Steiner, Pallawi Torka, Kevin A. David, Jennifer Kimberly Lue, Paul A. Hamlin, Alison J. Moskowitz, Lorenzo Falchi, J. Erika Haydu, P. Connor Johnson, Joanna Mi, Jessica Pendleton, A. Labarre, Rosalba Martignetti, Sean F. Plummer, Maria Chabowska, Walter Ramos Amador, Neena Mahajan, Morgan Choma, Clare Grieve, Rayna N. Garcia, Hailey E. Kelly, Ella Mallinger, James O’Grady, Bernadette Beatty, Michelle M. Adams, Athina Apazidis, Aileen Cleary Cohen, Mina Shahkarami, Allison P. Jacob, Omar Abdel‐Wahab, Andrew D. Zelenetz · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-205697 · 被引用次数：11 · 研究领域：Chronic Lymphocytic Leukemia Research、Lymphoma Diagnosis and Treatment、Chronic Myeloid Leukemia Treatments

Background: Venetoclax-obinutuzumab induces durable undetectable MRD at ≤10-4 (uMRD4) in treatment-naïve CLL (MRD4-free survival of 21 months [mo] for patients (pts) with uMRD4) (Al-Sawaf JCO 2021). Zanubrutinib is a second-generation BTKi with superior PFS and safety compared with ibrutinib (Brown NEJM 2023). BOVen (zanubrutinib, obinutuzumab, venetoclax) was well-tolerated with frequent uMRD in pts with previously untreated CLL (Soumerai Lancet Haem 2021). In the initial report, response kinetics defined as ΔMRD400 (≥400-fold reduction in peripheral blood [PB] MRD level by immunosequencing from baseline to cycle 5 day 1) predicted more durable uMRD4 despite less time on therapy. Herein, we present 5-year follow-up of BOVen in treatment-naïve CLL, safety and efficacy of retreatment with zanubrutinib-venetoclax, and the impact of ΔMRD400 on outcomes. Methods: In this multicenter, phase 2 trial (NCT03824483), eligible pts had CLL/SLL requiring first-line treatment (iwCLL 2018), ECOG PS ≤2, ANC ≥1,000/l and PLT ≥75,000/l (PLT ≥20,000 and no ANC requirement if due to CLL). Informed consent was obtained from all pts. BOVen was administered in 28-day cycles: Zanubrutinib 160 mg by mouth (PO) twice daily starting D1; Obinutuzumab 1000 mg intravenously (IV) on D1 (split D1-2 if ALC ≥25,000/ul or LN ≥5cm), 8, and 15 of C1, and D1 of C2-8; Venetoclax ramp up started on C3D1 (target 400 mg PO daily). Treatment consisted of 8-24 cycles with duration determined by MRD (flow cytometry; MR...