Zanubrutinib for the treatment of patients with Waldenström macroglobulinemia: 3 years of follow-up.

Autor:	Trotman J; Department of Haematology, Concord Repatriation General Hospital and Faculty of Medicine and Health, University of Sydney, Concord, NSW, Australia., Opat S; Clinical Haematology Unit, Monash Health and Monash University, Clayton, VIC, Australia., Gottlieb D; Faculty of Medicine and Health, University of Sydney, Westmead Hospital Sydney, Sydney, NSW, Australia., Simpson D; North Shore Hospital, Auckland, New Zealand.; BeiGene USA, Inc., San Mateo, CA., Marlton P; Department of Haematology, Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD, Australia.; University of Queensland Faculty of Medicine, Brisbane, QLD, Australia., Cull G; Haematology Department, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.; Department of Lymphoma/Myeloma, University of Western Australia, Perth, WA, Australia., Munoz J; Banner MD Anderson Cancer Center, Gilbert, AZ., Tedeschi A; ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy., Roberts AW; Haematology Department, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia., Seymour JF; Haematology Department, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia.; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia., Atwal SK; BeiGene USA, Inc., San Mateo, CA., Yu Y; BeiGene (Shanghai) Co., Ltd., Shanghai, China; and., Novotny W; BeiGene USA, Inc., San Mateo, CA., Holmgren E; BeiGene USA, Inc., San Mateo, CA., Tan Z; BeiGene (Shanghai) Co., Ltd., Shanghai, China; and., Hilger JD; BeiGene USA, Inc., San Mateo, CA., Huang J; BeiGene USA, Inc., San Mateo, CA., Tam CS; Haematology Department, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia.; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.; St. Vincent's Hospital, Fitzroy, VIC, Australia.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2020 Oct 29; Vol. 136 (18), pp. 2027-2037.
DOI:	10.1182/blood.2020006449
Abstrakt:	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. (© 2020 by The American Society of Hematology.)
Databáze:	MEDLINE
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