Zanubrutinib monotherapy in relapsed/refractory indolent non-Hodgkin lymphoma

Tycel Phillips, Henry Chan, Constantine S Tam, Alessandra Tedeschi, Patrick Johnston, Sung Yong Oh, Stephen Opat, Hyeon-Seok Eom, Heather Allewelt, Jennifer C Stern, Ziwen Tan, William Novotny, Jane Huang, Judith Trotman, Tycel Phillips, Henry Chan, Constantine S Tam, Alessandra Tedeschi, Patrick Johnston, Sung Yong Oh, Stephen Opat, Hyeon-Seok Eom, Heather Allewelt, Jennifer C Stern, Ziwen Tan, William Novotny, Jane Huang, Judith Trotman

Abstract

Outcomes for marginal zone lymphoma (MZL) and follicular lymphoma (FL) remain suboptimal, owing to the limited number of approved agents and the incurable nature of the diseases. BGB-3111-AU-003 was a phase 1/2, open-label, multicenter, single-agent study of the selective Bruton's tyrosine kinase inhibitor zanubrutinib in 385 patients with B-cell malignancies. Here, we present safety and efficacy outcomes for the 53 enrolled patients with relapsed/refractory MZL (n = 20) and relapsed/refractory FL (n = 33), all of whom were enrolled during the part 2 dose expansion, and therefore received zanubrutinib at the recommended phase 2 dose. Treatment with zanubrutinib was generally well tolerated, with most adverse events being ≤ grade 2. Atrial fibrillation/flutter was not reported. Two patients required dose reduction, and 4 patients discontinued treatment because of adverse events. Response was assessed by an independent review committee for MZL and the investigators for FL, per Lugano 2014 classification for non-Hodgkin lymphoma. In patients with MZL, the overall response rate (ORR) was 80%, and the complete response (CR) rate was 20%. With median follow-up of 33.8 months, median progression-free survival (PFS) was not reached. In patients with FL, the ORR was 36.4%, and the CR rate was 18.2%. After a median follow-up of 33.9 months, median PFS was 10.4 months. In conclusion, the results of this study suggest a favorable benefit-risk profile and support zanubrutinib as a potentially meaningful addition to available therapies for patients with relapsed/refractory MZL and FL. This trial was registered at www.clinicaltrials.gov as #NCT02343120.

© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Kaplan-Meier plots. (A) DOR with zanubrutinib treatment per IRC assessment for patients with MZL. (B) PFS with zanubrutinib per IRC assessment for patients with MZL. (C) DOR with zanubrutinib per investigator assessment for patients with FL. (D) PFS with zanubrutinib per investigator assessment for patients with FL.

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