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Clinical Trial
. 2025 Apr;121(4):483-493.
doi: 10.1007/s12185-025-03925-1. Epub 2025 Feb 17.

Zanubrutinib in Japanese treatment-naive and relapsed/refractory patients with Waldenström macroglobulinemia and CLL/SLL

Koji Izutsu  1 , Takayuki Ishikawa  2 , Kazuyuki Shimada  3 , Kohmei Kubo  4 , Takeshi Kondo  5 , Katsuya Fujimoto  6 , Tomoaki Fujisaki  7 , Shingo Kurahashi  8 , Koji Nagafuji  9 , Rika Sakai  10 , Tatsuro Jo  11 , Tomonori Nakazato  12 , Kazutaka Sunami  13 , Senji Kasahara  14 , Aileen Cohen  15 , Motohisa Takai  15 , Jinhua Zhong  16 , Masahiro Takeuchi  17
Affiliations
Clinical Trial

Zanubrutinib in Japanese treatment-naive and relapsed/refractory patients with Waldenström macroglobulinemia and CLL/SLL

Koji Izutsu et al. Int J Hematol. 2025 Apr.

Abstract

Zanubrutinib is a selective second-generation Bruton tyrosine kinase inhibitor approved in various B-cell malignancies globally. The phase 1/2 BGB-3111-111 study evaluated the efficacy and safety of zanubrutinib 160 mg twice daily orally in Japanese patients with treatment-naive or relapsed/refractory mature B-cell malignancies. Here, efficacy results from Part 2 in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; n = 19) and Waldenström macroglobulinemia (WM; n = 19), and safety results from Parts 1 (N = 6) and 2 (N = 49) are presented, with the first dose between 30 January, 2020, and 31 October, 2022. As of 10 May, 2023, investigator-assessed overall response rates were 100% (19/19) and 94.7% (18/19) in CLL/SLL and WM, respectively, with median follow-up of 27.9 and 26.8 months; 24-month progression-free survival rates were 71.4% and 100% in treatment-naive and relapsed/refractory CLL/SLL and 83.9% and 100% in treatment-naive and relapsed/refractory WM, respectively. In patients with B-cell malignancies, any-grade treatment-emergent adverse events (TEAEs) occurred in 53 (96.4%) and serious TEAEs in 18 (32.7%). Common TEAEs were platelet count decreased (18.2%), pyrexia (18.2%), COVID-19 (14.5%), and neutrophil count decreased (12.7%). With median follow-up > 2 years, zanubrutinib demonstrated durable efficacy in Japanese patients with CLL/SLL or WM and a favorable safety profile consistent with global phase 3 studies.

Keywords: Bruton tyrosine kinase; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Japanese; Waldenström Macroglobulinemia; Zanubrutinib.

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Conflict of interest statement

Declarations. Conflict of interest: Takayuki Ishikawa, Kazuyuki Shimada, Kohmei Kubo, Takeshi Kondo, Tomoaki Fujisaki, Shingo Kurahashi, Rika Sakai, Tatsuro Jo, Tomonori Nakazato, Masahiro Takeuchi: No conflict of interest to disclose. Koji Izutsu: Honoraria from Ono Pharmaceutical, Janssen; research funding from AstraZeneca, AbbVie, Incyte, Bristol Myers Squibb, Novartis, Janssen, Yakult, Daiichi Sankyo, Chugai, BeiGene, Genmab. Katsuya Fujimoto: Research funding from Parexel International Co, Ltd, Insight Biosciences Japan, LLC. Kazutaka Sunami: Honoraria from Celgene, Bristol Myers Squibb, Takeda Pharmaceutical, Sanofi; research funding from Ono Pharmaceutical, MSD, Celgene, AbbVie G.K., Takeda Pharmaceutical, Sanofi, Bristol Myers Squibb, Daiichi Sankyo, Alexion Pharma, GSK, Otsuka Pharmaceutical, Novartis Pharma, Astellas, Amgen, Janssen Pharma, Chugai Pharmaceutical, Kyowa Kirin, Pfizer. Senji Kasahara: Honoraria from Daiichi Sankyo; research funding from Novartis Pharma, Astellas Pharma, Daiichi Sankyo. Aileen Cohen: Consultant and equity holder with BeiGene. Motohisa Takai, Jinhua Zhong: Employment and stock options from BeiGene. Koji Nagafuji: An editor of International Journal of Hematology during the review process.

Figures

Fig. 1
Fig. 1
Patient Disposition. Data cutoff: 10 May 2023. a Includes patients from Part 1 (FL, n = 2; MZL, n = 1; MCL, n = 1) and the Part 2 R/R MCL cohort (n = 11). AE adverse event; CLL/SLL chronic lymphocytic leukemia/small lymphocytic lymphoma; FL follicular lymphoma; MCL mantle cell lymphoma; MZL marginal zone lymphoma; PD progressive disease; R/R relapsed/refractory; TN treatment naive; WM Waldenström macroglobulinemia
Fig. 2
Fig. 2
Best Overall Response Assessed by Investigator in Part 2 in Patients With A CLL/SLL and B WMa. aData cutoff: 10 May 2023. bEstimated using Clopper-Pearson method. CLL/SLL chronic lymphocytic leukemia/small lymphocytic lymphoma; CR complete response; MR minor response; ORR overall response rate; PD progressive disease; PR partial response; PR-L partial response with lymphocytosis; R/R relapsed/refractory; SD stable disease; TN treatment naive; VGPR very good partial response; WM Waldenström macroglobulinemia
Fig. 3
Fig. 3
Investigator-Assessed PFS in Part 2 Patients With A CLL/SLL and B WMa. a Data cutoff: 10 May 2023. CLL/SLL chronic lymphocytic leukemia/small lymphocytic lymphoma; PFS progression-free survival; R/R relapsed/refractory; TN treatment naive; WM Waldenström macroglobulinemia
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