Zanubrutinib for the treatment of patients with Waldenstrom macroglobulinemia: three years of follow-up
- Author(s)
- Trotman, J; Opat, S; Gottlieb, DJ; Simpson, D; Marlton, P; Cull, G; Munoz, J; Tedeschi, A; Roberts, AW; Seymour, JF; Atwal, SK; Yu, Y; Novotny, W; Holmgren, EB; Tan, Z; Hilger, J; Huang, J; Tam, C;
- Journal Title
- Blood
- Publication Type
- Journal epub ahead of print
- Abstract
- Inhibitors of Bruton's tyrosine kinase (BTK) have established therapeutic activity in patients with Waldenstrom macroglobulinemia (WM). Zanubrutinib, a potent and selective BTK inhibitor, was evaluated in a phase 1/2 study in patients with WM who were either treatment-naive (TN) or had relapsed/refractory (R/R) disease. Patients had disease requiring treatment per International Workshop on Waldenstrom Macroglobulinemia (IWWM) criteria. Treatment was oral zanubrutinib 160 mg twice daily (n=50) or 320 mg once daily (n=23). Efficacy endpoints included overall response rate (ORR) and very good partial response/complete response (VGPR/CR) rates per IWWM-6 criteria (with modification of VGPR definition based on Treon 2015). Between September 2014 and March 2018, 77 patients (24 TN and 53 R/R) began treatment. At a median follow-up of 36.0 months for patients with R/R disease and 23.5 months for TN, 72.7% remained on treatment. Reasons for treatment discontinuation included any adverse events in 13.0% of patients (1 treatment related), disease progression (10.4%), and other (3.9%). The ORR was 95.9%, and the VGPR/CR rate was 45.2%, which increased over time: 20.5% at 6 months, 32.9% at 12 months, and 43.8% at 24 months. Estimated 3-year progression-free survival rate was 80.5%, and overall survival rate was 84.8%. Adverse events of interest included contusion (32.5%, all grade 1), neutropenia (18.2%), major hemorrhage (3.9%), atrial fibrillation/flutter (5.2%), and grade 3 diarrhea (2.6%). Long-term treatment with single-agent zanubrutinib resulted in deep and durable responses in some patients with WM. The safety profile of long-term zanubrutinib therapy in these patients was acceptable.
- Publisher
- ASH
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 32698195
- Publisher's Version
- https://doi.org/10.1182/blood.2020006449
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-08-05 10:22:52
Last Modified: 2020-08-05 10:24:21