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Zanubrutinib for the treatment of patients with Waldenström macroglobulinemia: 3 years of follow-up
- Source :
- Blood
- Publication Year :
- 2020
-
Abstract
- Inhibitors of Bruton’s tyrosine kinase (BTK) have established therapeutic activity in patients with Waldenström 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-naïve (TN) or had relapsed/refractory (R/R) disease. Patients had disease requiring treatment per International Workshop on Waldenström Macroglobulinemia (IWWM) criteria. Treatment was 160 mg of oral zanubrutinib 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 published previously). 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. This trial was registered at www.clinicaltrials.gov as #NCT02343120.
- Subjects :
- Adult
Male
medicine.medical_specialty
Immunology
Salvage therapy
Antineoplastic Agents
Neutropenia
Biochemistry
Gastroenterology
Cohort Studies
chemistry.chemical_compound
Refractory
Piperidines
Internal medicine
medicine
Humans
Adverse effect
Survival rate
Aged
Aged, 80 and over
Salvage Therapy
Errata
business.industry
Waldenstrom macroglobulinemia
Cell Biology
Hematology
Middle Aged
medicine.disease
Prognosis
Discontinuation
Survival Rate
Pyrimidines
chemistry
Drug Resistance, Neoplasm
Ibrutinib
Pyrazoles
Female
Neoplasm Recurrence, Local
Waldenstrom Macroglobulinemia
business
Follow-Up Studies
Subjects
Details
- ISSN :
- 15280020
- Volume :
- 136
- Issue :
- 18
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....a045b7afa5102ba19db1d559d775c81f