Trium study: Exploring MRD-guided triplet therapy with sonrotoclax, zanubrutinib, and CD20mab in Untreated Mantle Cell Lymphoma: A prospective, multicenter, Phase II Study

作者：Peiqi Zhao, Yulan Zhou, Lihua Qiu, Yinan Gao, Zhengzi Qian, Xingli Zou, Pan Zhao, Jianxia He, Fei Li, Huilai Zhang · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-1809 · 被引用次数：1 · 研究领域：Lymphoma Diagnosis and Treatment、Cutaneous lymphoproliferative disorders research、Protein Degradation and Inhibitors

Abstract Background Targeted therapy-based induction regimens provide novel treatment options for newly diagnosed mantle cell lymphoma (MCL). Recent studies have demonstrated the promising efficacy of triple-drug combinations comprising BCL-2 inhibitors, BTK inhibitors, and CD20 monoclonal antibodies (e.g., IVO, IVR, AVO, ZVO). Sonrotoclax (BGB-11417), a next-generation BCL-2 inhibitor, exhibits higher selectivity and pharmacological potency than venetoclax, with a shorter half-life and no drug accumulation. Zanubrutinib, a next-generation BTK inhibitor, has shown favorable safety and efficacy profiles in treatment-naïve (TN) MCL patients. Objective To evaluate the efficacy and safety of sonrotoclax-containing, chemotherapy-free triplet induction therapy in TN MCL. Methods This open-label, single-arm, multicenter trial (NCT06463691) enrolled treatment-naïve MCL patients. Patients received zanubrutinib (160 mg BID) plus zuberitamab, a novel CD20mab with enhanced antibody-dependent cellulal cytotoxicity, for 2 cycles as lead-in treatment. Sonrotoclax was added at Cycle 3 Day 1 with dose escalation to target 320 mg daily. Triplet therapy continued through Cycle 12. After induction, patients achieving complete remission (CR) with undetectable minimal residual disease (MRD) without high-risk features would receive 1 year of sonrotoclax plus zanubrutinib, followed by 1 year of zanubrutinib monotherapy. Patients assessed as partial response (PR), or MRD-positive, or with high-risk, ...