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. Estima...Continue Reading
References
Apr 30, 2003·Seminars in Oncology·Roger G OwenMeletios A Dimopoulos
May 14, 2011·British Journal of Haematology·Steven P TreonBarry Turnbull
Aug 31, 2012·The New England Journal of Medicine·Steven P TreonZachary R Hunter
Oct 10, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ranjana H AdvaniNathan H Fowler
Nov 16, 2012·British Journal of Haematology·Roger G OwenUNKNOWN VIth International Workshop on Waldenström macroglobulinaemia
Feb 21, 2014·Blood·Steven P TreonZachary R Hunter
Aug 21, 2014·Leukemia·S KamelC S Tam
Oct 12, 2014·Blood·Marie LevadeBernard Payrastre
Nov 6, 2014·British Journal of Haematology·Yang CaoSteven P Treon
Apr 9, 2015·The New England Journal of Medicine·Steven P TreonRanjana H Advani
May 24, 2015·Blood·Steven P Treon
Jan 23, 2016·International Journal of Laboratory Hematology·A AlbitarM Albitar
Dec 14, 2016·The Lancet Oncology·Meletios A DimopoulosUNKNOWN iNNOVATE Study Group and the European Consortium for Waldenström's Macroglobulinemia
Sep 14, 2017·Leukemia & Lymphoma·Chloe Pek Sang TangConstantine Tam
Nov 29, 2017·British Journal of Haematology·Steven P TreonJorge J Castillo
Jul 26, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Steven P TreonJorge J Castillo
Oct 18, 2018·American Journal of Hematology·Morie A Gertz
Jul 4, 2019·British Journal of Haematology·Jorge J CastilloSteven P Treon
Jul 26, 2019·Blood·Constantine S TamAndrew W Roberts
Dec 24, 2019·Blood Advances·Gasim DobieDenise E Jackson
Citations
Feb 23, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Steven P TreonJorge J Castillo
Oct 30, 2020·Blood·Prashant Kapoor, Steven P Treon
Dec 8, 2020·Blood Advances·Meletios DimopoulosConstantine S Tam
Dec 11, 2020·Expert Review of Hematology·Kenneth J C Lim, Constantine S Tam
Jan 15, 2021·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Roger G Owen
Dec 15, 2020·Platelets·Maan H HarbiMark R Thomas
Dec 29, 2020·American Journal of Hematology·Morie A Gertz
Feb 12, 2021·Leukemia & Lymphoma·Andrew R BranaganJorge J Castillo
Feb 23, 2021·Therapeutic Advances in Hematology·Ioannis Ntanasis-StathopoulosMeletios A Dimopoulos
Nov 18, 2020·Blood·M K GandhiC Keane
Mar 30, 2021·Frontiers in Cell and Developmental Biology·H Yesid EstupiñánC I Edvard Smith
Apr 22, 2021·Current Treatment Options in Allergy·Melanie C Dispenza
Apr 29, 2021·American Journal of Hematology·Jithma P AbeykoonPrashant Kapoor
May 5, 2021·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Soi C LawMaher K Gandhi
Jun 24, 2021·Leukemia & Lymphoma·Ying C OuSrikumar Sahasranaman
Aug 25, 2021·Current Treatment Options in Oncology·Shayna SarosiekJorge J Castillo
Sep 12, 2021·Aging·Xianhuo WangHuilai Zhang
Sep 8, 2021·Expert Review of Clinical Pharmacology·Constantine S TamStephen Opat
Sep 25, 2021·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Donald C Moore
Oct 26, 2021·Current Treatment Options in Oncology·Lori A Leslie