TY - JOUR
T1 - The MAGNOLIA Trial
T2 - Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma
AU - Opat, Stephen
AU - Tedeschi, Alessandra
AU - Linton, Kim
AU - McKay, Pamela
AU - Hu, Bei
AU - Chan, Henry
AU - Jin, Jie
AU - Sobieraj-Teague, Magdalena
AU - Zinzani, Pier Luigi
AU - Coleman, Morton
AU - Thieblemont, Catherine
AU - Browett, Peter
AU - Ke, Xiaoyan
AU - Sun, Mingyuan
AU - Marcus, Robert
AU - Portell, Craig A.
AU - Ardeshna, Kirit
AU - Bijou, Fontanet
AU - Walker, Patricia
AU - Hawkes, Eliza A.
AU - Mapp, Sally
AU - Ho, Shir-Jing
AU - Talaulikar, Dipti
AU - Zhou, Ke Shu
AU - Co, Melannie
AU - Li, Xiaotong
AU - Zhou, Wenxiao
AU - Cappellini, Massimo
AU - Tankersley, Chris
AU - Huang, Jane
AU - Trotman, Judith
N1 - ©2021 The Authors; Published by the American Association for Cancer Research.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
KW - Protein Kinase Inhibitors/adverse effects
KW - Pyrimidines
KW - Pyrazoles
KW - Humans
KW - Piperidines
KW - Magnolia
KW - Lymphoma, B-Cell, Marginal Zone
U2 - 10.1158/1078-0432.CCR-21-1704
DO - 10.1158/1078-0432.CCR-21-1704
M3 - Article
C2 - 34526366
AN - SCOPUS:85120056629
SN - 1078-0432
VL - 27
SP - 6323
EP - 6332
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 23
ER -
