The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma

• Published in: Clinical cancer research 2021-12, Vol.27 (23), p.6323-6332
• Main Authors: Opat, Stephen, Tedeschi, Alessandra, Linton, Kim, McKay, Pamela, Hu, Bei, Chan, Henry, Jin, Jie, Sobieraj-Teague, Magdalena, Zinzani, Pier Luigi, Coleman, Morton, Thieblemont, Catherine, Browett, Peter, Ke, Xiaoyan, Sun, Mingyuan, Marcus, Robert, Portell, Craig A, Ardeshna, Kirit, Bijou, Fontanet, Walker, Patricia, Hawkes, Eliza A, Mapp, Sally, Ho, Shir-Jing, Talaulikar, Dipti, Zhou, Ke-Shu, Co, Melannie, Li, Xiaotong, Zhou, Wenxiao, Cappellini, Massimo, Tankersley, Chris, Huang, Jane, Trotman, Judith
• Format: Article
• Language: English
• Subjects: Clinical Trials: Targeted Therapy; Humans; Lymphoma, B-Cell, Marginal Zone; Magnolia; Piperidines; Protein Kinase Inhibitors - adverse effects; Pyrazoles; Pyrimidines
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-21-1704

Marginal zone lymphoma (MZL) is an uncommon non-Hodgkin lymphoma with malignant cells that exhibit a consistent dependency on B-cell receptor signaling. We evaluated the efficacy and safety of zanubrutinib, a next-generation selective Bruton tyrosine kinase inhibitor, in patients with relapsed/refractory (R/R) MZL. Patients with R/R MZL were enrolled in the phase II MAGNOLIA (BGB-3111-214) study. The primary endpoint was overall response rate (ORR) as determined by an independent review committee (IRC) based on the Lugano 2014 classification. Sixty-eight patients were enrolled. After a median follow-up of 15.7 months (range, 1.6 to 21.9 months), the IRC-assessed ORR was 68.2% and complete response (CR) was 25.8%. The ORR by investigator assessment was 74.2%, and the CR rate was 25.8%. The median duration of response (DOR) and median progression-free survival (PFS) by independent review was not reached. The IRC-assessed DOR rate at 12 months was 93.0%, and IRC-assessed PFS rate was 82.5% at both 12 and 15 months. Treatment was well tolerated with the majority of adverse events (AE) being grade 1 or 2. The most common AEs were diarrhea (22.1%), contusion (20.6%), and constipation (14.7%). Atrial fibrillation/flutter was reported in 2 patients; 1 patient had grade 3 hypertension. No patient experienced major hemorrhage. In total, 4 patients discontinued treatment due to AEs, none of which were considered treatment-related by the investigators. Zanubrutinib demonstrated high ORR and CR rate with durable disease control and a favorable safety profile in patients with R/R MZL.