Preliminary safety and efficacy of boven (Zanubrutinib, Obinutuzumab, and Venetoclax) as frontline therapy for older patients with Mantle Cell Lymphoma

作者：Anita Ashok Kumar, Jacob Drobnyk Soumerai, Reem Karmali, Jeremy S. Abramson, Jeffrey A. Barnes, Bernadette Beatty, Jason Brecher, Philip C. Caron, Kenneth Robert Carson, Maria Chabowska, Madelyn Coogan, Jayne Coyle, Kevin A. David, Meemanage De Zoysa, Ahmet Doǧan, Zachary Drew Epstein-Peterson, Paola Ghione, Cameron Gordan, Leo I. Gordon, J. Erika Haydu, Ephraim P. Hochberg, Patrick Connor Johnson, Ashlee Joseph, Akshata Kakolu, Alyssa Labarre, Carissa Laudati, Jennifer Kimberly Lue, Shuo Ma, Rosalba Martignetti, Colette Ngozi Owens, Olivia Maas, Joanna Mi, Rachel Nazzaro, James O’Grady, Jessica Pendleton, Gilles Salles, Venkatraman Seshan, Natalie Slupe, Pallawi Torka, Andrew David Zelenetz · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-888 · 被引用次数：5 · 研究领域：Lymphoma Diagnosis and Treatment、CAR-T cell therapy research、Cutaneous lymphoproliferative disorders research

Abstract Background: Frontline mantle cell lymphoma (MCL) treatments are rapidly evolving with incorporation of targeted therapies. We previously demonstrated the safety and efficacy of the BOVen triplet (Zanubrutinib, Obinutuzumab, and Venetoclax) in high-risk pts with TP53-mutant MCL (Kumar Blood 2025). In this phase II, multi-center, investigator-initiated clinical trial, we evaluated the safety and efficacy of BOVen for older MCL pts using a minimal residual disease (MRD)-driven, time-limited approach. Methods: Eligible pts had previously untreated MCL, requiring therapy, ≥65 years (yrs) of age or with comorbidities precluding autologous stem cell transplantation, and ECOG PS ≤2, ANC >1, PLT >75, HGB ≥9 (unless due to MCL). BOVen was administered in 28D cycles: Zanubrutinib (Zanu) 160 mg PO BID starting D1; Obinutuzumab (Obin) 1000 mg IV D1 or split D1-2, 8, 15 of C1, and D1 of C2-8; and Venetoclax (Ven) with standard ramp up dosing initiated C3D1 (target 400 mg QD). The minimum treatment duration was 24 cycles and if uMRD6 complete response (CR) was achieved after 24 cycles, then Zanu and Ven were stopped. The primary endpoint was 3-year progression-free survival (PFS). Responses were assessed per Lugano criteria. MRD was assessed serially using Adaptive clonoSEQ®in peripheral blood (PB) and bone marrow (BM). Results: 50 pts were enrolled across 3 sites; data cut April 30, 2025. The median age at enrollment was 72 years (range 47-89); 1 patient was <65 years of age, but ...