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

in International journal of hematology by Koji Izutsu, Takayuki Ishikawa, Kazuyuki Shimada, Kohmei Kubo, Takeshi Kondo, Katsuya Fujimoto, Tomoaki Fujisaki, Shingo Kurahashi, Koji Nagafuji, Rika Sakai, Tatsuro Jo, Tomonori Nakazato, Kazutaka Sunami, Senji Kasahara, Aileen Cohen, Motohisa Takai, Jinhua Zhong, Masahiro Takeuchi

TLDR

  • Zanubrutinib demonstrated durable efficacy and a favorable safety profile in Japanese patients with CLL/SLL and WM, with high overall response rates and favorable progression-free survival rates.
  • Common treatment-emergent adverse events included platelet count decreased, pyrexia, COVID-19, and neutrophil count decreased, indicating a manageable safety profile.

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.

Overview

  • The study evaluated the efficacy and safety of zanubrutinib 160 mg twice daily in Japanese patients with treatment-naive or relapsed/refractory mature B-cell malignancies.
  • A total of 19 patients with CLL/SLL and 19 patients with WM received zanubrutinib in Part 2, with a median follow-up of 27.9 months (CLL/SLL) and 26.8 months (WM).
  • The study included patients who were treatment-naive or had relapsed/refractory disease, allowing for a comprehensive evaluation of zanubrutinib's efficacy in different patient populations.

Comparative Analysis & Findings

  • The investigator-assessed overall response rates for CLL/SLL and WM were 100% (19/19) and 94.7% (18/19), respectively, with a median follow-up of 27.9 and 26.8 months.
  • The 24-month progression-free survival rates for treatment-naive and relapsed/refractory CLL/SLL and WM were 71.4% and 100%, respectively.
  • Common treatment-emergent adverse events included platelet count decreased, pyrexia, COVID-19, and neutrophil count decreased.

Implications and Future Directions

  • The study demonstrates the efficacy of zanubrutinib in Japanese patients with CLL/SLL and WM, with a favorable safety profile consistent with global phase 3 studies.
  • Future studies can investigate the optimal dosing and scheduling of zanubrutinib, as well as its combination with other therapies, to further improve treatment outcomes.
  • The study highlights the importance of conducting clinical trials in diverse patient populations, including Japanese patients, to ensure that treatment options are effective and safe for all patients.
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