PMID- 35303070 OWN - NLM STAT- MEDLINE DCOM- 20220530 LR - 20220716 IS - 1528-0020 (Electronic) IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 139 IP - 21 DP - 2022 May 26 TI - Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study. PG - 3148-3158 LID - 10.1182/blood.2021014162 [doi] AB - Bruton tyrosine kinase (BTK) inhibitor is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL). Zanubrutinib, a highly selective BTK inhibitor, is approved for patients with MCL who have received >/=1 prior therapy. We report the long-term safety and efficacy results from the multicenter, open-label, phase 2 registration trial of zanubrutinib. Patients (n = 86) received oral zanubrutinib 160 mg twice daily. The primary endpoint was the overall response rate (ORR), assessed per Lugano 2014. After a median follow-up of 35.3 months, the ORR was 83.7%, with 77.9% achieving complete response (CR); the median duration of response was not reached. Median progression-free survival (PFS) was 33.0 months (95% confidence interval [CI], 19.4-NE). The 36-month PFS and overall survival (OS) rates were 47.6% (95% CI, 36.2-58.1) and 74.8% (95% CI, 63.7-83.0), respectively. The safety profile was largely unchanged with extended follow-up. Most common (>/=20%) all-grade adverse events (AEs) were neutrophil count decreased (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), white blood cell count decreased (33.7%), and platelet count decreased (32.6%); most were grade 1/2 events. Most common (>/=10%) grade >/=3 AEs were neutrophil count decreased (18.6%) and pneumonia (12.8%). Rates of infection, neutropenia, and bleeding were highest in the first 6 months of therapy and decreased thereafter. No cases of atrial fibrillation/flutter, grade >/=3 cardiac AEs, second primary malignancies, or tumor lysis syndrome were reported. After extended follow-up, zanubrutinib demonstrated durable responses and a favorable safety profile in R/R MCL. The trial is registered at ClinicalTrials.gov as NCT03206970. CI - (c) 2022 by The American Society of Hematology. FAU - Song, Yuqin AU - Song Y AD - Department of Lymphoma, Peking University Cancer Hospital & Institute (Beijing Cancer Hospital), Beijing, China. FAU - Zhou, Keshu AU - Zhou K AUID- ORCID: 0000-0001-5467-1377 AD - Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China. FAU - Zou, Dehui AU - Zou D AD - State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. FAU - Zhou, Jianfeng AU - Zhou J AD - Department of Hematology, Tongji Hospital, Tongji Medical College, Wuhan, China. FAU - Hu, Jianda AU - Hu J AD - Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China. FAU - Yang, Haiyan AU - Yang H AD - Department of Oncology, Zhejiang Cancer Hospital, Hangzhou, China. FAU - Zhang, Huilai AU - Zhang H AD - Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China. FAU - Ji, Jie AU - Ji J AD - Department of Hematology, West China Hospital of Sichuan University, Chengdu, China. FAU - Xu, Wei AU - Xu W AD - Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. FAU - Jin, Jie AU - Jin J AD - Department of Hematology, the First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China. FAU - Lv, Fangfang AU - Lv F AD - Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. FAU - Feng, Ru AU - Feng R AD - Department of Hematology, Nanfang Hospital of Southern Medical University, Guangzhou, China. FAU - Gao, Sujun AU - Gao S AD - Department of Hematology, Cancer Center, The First Hospital of Jilin University, Changchun, China. FAU - Guo, Haiyi AU - Guo H AD - BeiGene (Shanghai) Co., Ltd., Shanghai, China. FAU - Zhou, Lei AU - Zhou L AD - BeiGene (Beijing) Co., Ltd., Beijing, China; and. FAU - Huang, Jane AU - Huang J AD - BeiGene USA, Inc., San Mateo, CA. FAU - Novotny, William AU - Novotny W AD - BeiGene USA, Inc., San Mateo, CA. FAU - Kim, Pil AU - Kim P AD - BeiGene USA, Inc., San Mateo, CA. FAU - Yu, Yiling AU - Yu Y AD - BeiGene (Shanghai) Co., Ltd., Shanghai, China. FAU - Wu, Binghao AU - Wu B AD - BeiGene (Shanghai) Co., Ltd., Shanghai, China. FAU - Zhu, Jun AU - Zhu J AUID- ORCID: 0000-0003-3479-2547 AD - Department of Lymphoma, Peking University Cancer Hospital & Institute (Beijing Cancer Hospital), Beijing, China. LA - eng SI - ClinicalTrials.gov/NCT03206970 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Piperidines) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrazoles) RN - 0 (Pyrimidines) RN - AG9MHG098Z (zanubrutinib) SB - IM CIN - Blood. 2022 May 26;139(21):3103-3104. PMID: 35616990 MH - Adult MH - Humans MH - *Lymphoma, Follicular MH - *Lymphoma, Mantle-Cell/drug therapy/pathology MH - *Neutropenia/chemically induced MH - Piperidines MH - Protein Kinase Inhibitors/adverse effects MH - Pyrazoles/adverse effects MH - Pyrimidines/adverse effects MH - Treatment Outcome PMC - PMC9136878 EDAT- 2022/03/19 06:00 MHDA- 2022/05/31 06:00 PMCR- 2022/05/26 CRDT- 2022/03/18 17:16 PHST- 2021/11/10 00:00 [received] PHST- 2022/02/14 00:00 [accepted] PHST- 2022/03/19 06:00 [pubmed] PHST- 2022/05/31 06:00 [medline] PHST- 2022/03/18 17:16 [entrez] PHST- 2022/05/26 00:00 [pmc-release] AID - S0006-4971(22)00399-8 [pii] AID - 2022/BLD2021014162 [pii] AID - 10.1182/blood.2021014162 [doi] PST - ppublish SO - Blood. 2022 May 26;139(21):3148-3158. doi: 10.1182/blood.2021014162.