PMID- 34253577 OWN - NLM STAT- MEDLINE DCOM- 20220401 LR - 20230106 IS - 1557-3265 (Electronic) IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 27 IP - 20 DP - 2021 Oct 15 TI - A Phase II Trial of the Bruton Tyrosine-Kinase Inhibitor Zanubrutinib (BGB-3111) in Patients with Relapsed/Refractory Waldenstrom Macroglobulinemia. PG - 5492-5501 LID - 10.1158/1078-0432.CCR-21-0539 [doi] AB - PURPOSE: Although Bruton tyrosine kinase (BTK) inhibitors have demonstrated promising efficacy in patients with Waldenstrom macroglobulinemia (WM), data in Asian populations are scarce. This trial is the first to investigate the effect of a BTK inhibitor in Chinese patients with relapsed/refractory (R/R) WM. PATIENTS AND METHODS: Patients with R/R WM with at least one prior regimen were enrolled into this single-arm, multicenter, phase II study (NCT03332173) and received zanubrutinib 160 mg twice daily until disease progression or unacceptable toxicity. The primary endpoint was major response rate (MRR), as assessed by an independent review committee. Secondary endpoints included progression-free survival, overall response rate, duration of major response, and safety. RESULTS: Forty-four patients were enrolled. After a median follow-up of 33.0 (range, 3.2-36.5) months, MRR in all patients was 69.8%, with very good partial response or better in 32.6% of patients. All mutation groups benefited from zanubrutinib treatment (MRR in patients with MYD88 (L265P) mutation, 73%; MRR in patients with MYD88 wild type mutation, 50%). A higher response rate was seen in the MYD88 (L265P)/CXCR4 (WT) population, compared with the other populations. Median progression-free survival and median duration of major response were not reached. The most frequently reported grade >/=3 treatment-emergent adverse events (AEs) were neutrophil count decreased (31.8%), and platelet count decreased and pneumonia (20.5% each). No case of atrial fibrillation/flutter occurred. CONCLUSIONS: Zanubrutinib achieved a high rate of response that was durable and deep in patients with R/R WM across all subgroups, and potentially confers a positive benefit-risk profile for WM. CI - (c)2021 The Authors; Published by the American Association for Cancer Research. FAU - An, Gang AU - An G AD - National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Blood Diseases & Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. FAU - Zhou, Daobin AU - Zhou D AD - Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. FAU - Cheng, Shu AU - Cheng S AD - Department of Hematology, Shanghai Ruijin Hospital, Shanghai, China. FAU - Zhou, Keshu AU - Zhou K AD - Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China. FAU - Li, Jianyong AU - Li J AD - Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiansu Province Hospital, Nanjing, China. FAU - Zhou, Jianfeng AU - Zhou J AUID- ORCID: 0000-0002-1332-9230 AD - Department of Hematology, Tongji Hospital, Tongji Medical College, Wuhan, China. FAU - Xie, Liping AU - Xie L AD - Department of Hematology, West China Hospital of Sichuan University, Chengdu, China. FAU - Jin, Jie AU - Jin J AUID- ORCID: 0000-0003-4617-2601 AD - Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China. FAU - Zhong, Liye AU - Zhong L AD - Department of Hematology, Guangdong Provincial People's Hospital, Guangzhou, China. FAU - Yan, Lingzhi AU - Yan L AD - Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. FAU - Guo, Haiyi AU - Guo H AD - BeiGene Co., Ltd, Beijing, China. FAU - Du, Chenmu AU - Du C AD - BeiGene Co., Ltd, Beijing, China. FAU - Zhong, Jinhua AU - Zhong J AD - BeiGene Co., Ltd, Shanghai, China. FAU - Yu, Yiling AU - Yu Y AUID- ORCID: 0000-0002-7220-9693 AD - BeiGene Co., Ltd, Shanghai, China. FAU - Wu, Binghao AU - Wu B AD - BeiGene Co., Ltd, Shanghai, China. FAU - Qiu, Lugui AU - Qiu L AD - National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Blood Diseases & Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. qiulg@ihcams.ac.cn. LA - eng SI - ClinicalTrials.gov/NCT03332173 PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210712 PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Antineoplastic Agents) RN - 0 (Piperidines) RN - 0 (Pyrazoles) RN - 0 (Pyrimidines) RN - AG9MHG098Z (zanubrutinib) RN - EC 2.7.10.2 (Agammaglobulinaemia Tyrosine Kinase) SB - IM MH - Adult MH - Agammaglobulinaemia Tyrosine Kinase/*antagonists & inhibitors MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/*therapeutic use MH - Female MH - Humans MH - Male MH - Middle Aged MH - Piperidines/*therapeutic use MH - Pyrazoles/*therapeutic use MH - Pyrimidines/*therapeutic use MH - Recurrence MH - Waldenstrom Macroglobulinemia/*drug therapy PMC - PMC9401548 EDAT- 2021/07/14 06:00 MHDA- 2022/04/02 06:00 PMCR- 2022/08/24 CRDT- 2021/07/13 05:48 PHST- 2021/03/03 00:00 [received] PHST- 2021/05/14 00:00 [revised] PHST- 2021/07/02 00:00 [accepted] PHST- 2021/07/14 06:00 [pubmed] PHST- 2022/04/02 06:00 [medline] PHST- 2021/07/13 05:48 [entrez] PHST- 2022/08/24 00:00 [pmc-release] AID - 1078-0432.CCR-21-0539 [pii] AID - CCR-21-0539 [pii] AID - 10.1158/1078-0432.CCR-21-0539 [doi] PST - ppublish SO - Clin Cancer Res. 2021 Oct 15;27(20):5492-5501. doi: 10.1158/1078-0432.CCR-21-0539. Epub 2021 Jul 12.