PMID- 34152395
OWN - NLM
STAT- MEDLINE
DCOM- 20210624
LR  - 20210925
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 5
IP  - 12
DP  - 2021 Jun 22
TI  - Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma.
PG  - 2577-2585
LID - 10.1182/bloodadvances.2020004074 [doi]
AB  - Zanubrutinib, a highly selective Bruton tyrosine kinase inhibitor, was evaluated 
      in a phase 1/2 study in patients with various B-cell malignancies. In the 
      subgroup of patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL), 
      zanubrutinib was administered as 160 mg twice daily (n = 14), 320 mg once daily 
      (n = 18), or </=160 mg total dose (n = 5). Herein, we report results for patients 
      receiving a total daily dose of 320 mg (N = 32). Median study follow-up was 18.8 
      months. Eighteen patients discontinued treatment, 10 because of progressive 
      disease and 8 because of adverse events (AEs); 1 AE (peripheral edema) was 
      considered to be related to zanubrutinib treatment. The most common AEs were 
      diarrhea (43.8%), contusion (37.5%), constipation (31.3%), and upper respiratory 
      tract infection (31.3%). Infection was the most commonly reported AE of interest 
      (18.8% of patients experienced grade >/=3 infection). At least 1 AE of grade >/=3 was 
      reported in 59.4% of patients; grade >/=3 AEs that were reported in >2 patients 
      were anemia (12.5%), pneumonia (9.4%), and myalgia (9.4%). Overall response rate 
      was 84%, with 25% achieving a complete response. Median duration of response was 
      18.5 months. Median progression-free survival (PFS) was 21.1 months. Zanubrutinib 
      was well tolerated and demonstrated activity in patients with R/R MCL. The trial 
      is registered at www.clinicaltrials.gov as #NCT02343120.
CI  - (c) 2021 by The American Society of Hematology.
FAU - Tam, Constantine S
AU  - Tam CS
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
AD  - St Vincent's Hospital, Fitzroy, VIC, Australia.
AD  - Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, 
      Parkville, VIC, Australia.
AD  - Royal Melbourne Hospital, Parkville, VIC, Australia.
FAU - Opat, Stephen
AU  - Opat S
AD  - Monash Health, Clayton, VIC, Australia.
AD  - Department of Haematology, Monash University, Clayton, VIC, Australia.
FAU - Simpson, David
AU  - Simpson D
AD  - North Shore Hospital, Auckland, New Zealand.
AD  - BeiGene USA, Inc., San Mateo, CA.
FAU - Cull, Gavin
AU  - Cull G
AD  - Sir Charles Gairdner Hospital, Perth, WA, Australia.
AD  - Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, 
      Australia.
FAU - Munoz, Javier
AU  - Munoz J
AD  - Banner MD Anderson Cancer Center, Gilbert, AZ.
FAU - Phillips, Tycel J
AU  - Phillips TJ
AD  - Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI.
FAU - Kim, Won Seog
AU  - Kim WS
AD  - Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South 
      Korea.
FAU - Rule, Simon
AU  - Rule S
AD  - Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom.
FAU - Atwal, Siminder Kaur
AU  - Atwal SK
AD  - BeiGene USA, Inc., San Mateo, CA.
FAU - Wei, Rachel
AU  - Wei R
AD  - BeiGene USA, Inc., San Mateo, CA.
FAU - Novotny, William
AU  - Novotny W
AD  - BeiGene USA, Inc., San Mateo, CA.
FAU - Huang, Jane
AU  - Huang J
AD  - BeiGene USA, Inc., San Mateo, CA.
FAU - Wang, Michael
AU  - Wang M
AUID- ORCID: 0000-0001-9748-5486
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX; and.
FAU - Trotman, Judith
AU  - Trotman J
AUID- ORCID: 0000-0001-8009-4593
AD  - Concord Repatriation Hospital, The University of Sydney, Sydney, NSW, Australia.
LA  - eng
SI  - ClinicalTrials.gov/NCT02343120
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Piperidines)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
RN  - AG9MHG098Z (zanubrutinib)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Lymphoma, Mantle-Cell/drug therapy
MH  - Piperidines
MH  - Pyrazoles
MH  - Pyrimidines/adverse effects
PMC - PMC8270663
COIS- Conflict-of-interest disclosure: C.S.T. receives research funding from Janssen 
      and AbbVie and honoraria from Janssen, AbbVie, BeiGene, Novartis, and Roche. S.O. 
      has acted as a consultant/advisor for AbbVie, Janssen, Gilead, Roche, 
      Mundipharma, Merck, Bristol Myers Squibb, and Celgene; has received research 
      funding from AbbVie, BeiGene, Janssen, Gilead, Roche, Celgene, and Epizyme; and 
      has received honoraria from AbbVie, Janssen, Gilead, Roche, Mundipharma, Merck, 
      Bristol Myers Squibb, and Celgene. D.S. is an employee of and has equity 
      ownership in BeiGene; has received honoraria from AbbVie, Janssen, and Roche; has 
      received research funding from AbbVie, Amgen, BeiGene, Celgene, Roche, MSD, 
      Acerta, Pharmacyclics, Sanofi, and GSK; and has received travel expenses from 
      AbbVie. G.C. has received research funding from BeiGene, Acerta, and 
      Glycomimetics. J.M. has received honoraria from Kyowa and Seattle Genetics; has 
      acted as a consultant/advisor for Pharmacyclics, Bayer, Gilead/Kite Pharma, 
      Pfizer, Janssen, Juno/Celgene, Bristol Myers Squibb, Kyowa, Alexion, BeiGene, 
      Fosunkite, Innovent, and Seattle Genetics; has been a member of the speakers' 
      bureau for Gilead/Kite Pharma, Kyowa, Bayer, Pharmacyclics/Janssen, Seattle 
      Genetics, Acrotech, BeiGene, and Verastem; and has received research funding from 
      Kite Pharma, Celgene, Portola, Incyte, Genentech, Pharmacyclics, Seattle 
      Genetics, Janssen, and Millennium. T.J.P. has acted as a consultant/advisor for 
      Bayer, Gilead, Seattle Genetics, Genentech, Incyte, and Pharmacyclics and has 
      received research funding from Pharmacyclics and AbbVie. W.S.K. has received 
      research funding from Roche, Takeda, Mundipharma, J&J, Celltrion, Kyowa Kirin, 
      and Donga. S.R. has received research funding from Janssen and has acted as a 
      consultant/advisor for Janssen, Kite, Sunesis, AstraZeneca, and Roche. S.K.A. is 
      an employee of and has equity ownership in BeiGene. R.W. is an employee of and 
      has equity ownership in BeiGene. W.N. is an employee of and has equity ownership 
      in BeiGene. J.H. is an employee of, has a leadership role with, and has equity 
      ownership in BeiGene. M.W. has equity ownership in MORE Health; has received 
      honoraria from Pharmacyclics, Janssen, AstraZeneca, OMI, Targeted Oncology, and 
      OncLive; has acted as a consultant/advisor for Pharmacyclics, Celgene, Janssen, 
      AstraZeneca, MORE Health, Pulse Biosciences, Nobel Insights, Guidepoint Global, 
      Kite Pharma, Juno, Celgene, and Loxo Oncology; has received research funding from 
      Pharmacyclics, Janssen, AstraZeneca, Kite Pharma, Juno, Celgene, Loxo Oncology, 
      VelosBio, and Verastem; and has received travel expenses from Janssen, 
      Pharmacyclics, Celgene, OMI, Kite Pharma, and AstraZeneca. J.T. has received 
      research funding from BeiGene, Roche, Pharmacyclics, Celgene, and Takeda.
EDAT- 2021/06/22 06:00
MHDA- 2021/06/25 06:00
PMCR- 2021/06/21
CRDT- 2021/06/21 12:20
PHST- 2020/12/22 00:00 [received]
PHST- 2021/04/08 00:00 [accepted]
PHST- 2021/06/21 12:20 [entrez]
PHST- 2021/06/22 06:00 [pubmed]
PHST- 2021/06/25 06:00 [medline]
PHST- 2021/06/21 00:00 [pmc-release]
AID - S2473-9529(21)00340-2 [pii]
AID - 2021/ADV2020004074 [pii]
AID - 10.1182/bloodadvances.2020004074 [doi]
PST - ppublish
SO  - Blood Adv. 2021 Jun 22;5(12):2577-2585. doi: 10.1182/bloodadvances.2020004074.