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

Abstract

Purpose: 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 and methods: 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.

Results: 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.

Conclusions: Zanubrutinib demonstrated high ORR and CR rate with durable disease control and a favorable safety profile in patients with R/R MZL.

Figure 1.

A, Kaplan–Meier plot of duration of response with zanubrutinib per IRC assessment based on Lugano classification (15) for patients with MZL in the MAGNOLIA study (BGB-3111–214). Only patients with either PR or CR were included. B, Kaplan–Meier plot of PFS with zanubrutinib per IRC assessment based on Lugano classification (15) for patients with MZL in the MAGNOLIA study (BGB-3111–214). CIs were calculated using a generalized Brookmeyer and Crowley method.

Figure 2.

Forest plot representing subgroup analysis of ORR per IRC assessment based on Lugano classification (15) for patients with MZL in the MAGNOLIA study (BGB-3111–214). CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone. ^aTwo-sided Clopper–Pearson 95% CIs for ORR.

Figure 3.

ORR per IRC assessment based on Lugano classification (15) for MZL patients in the MAGNOLIA study (BGB-3111–214).