PMID- 33967195
OWN - NLM
STAT- MEDLINE
DCOM- 20210603
LR  - 20230813
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 134
IP  - 11
DP  - 2021 May 6
TI  - Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin 
      lymphoma: a multicenter, open-label, single-arm, phase 3 study.
PG  - 1299-1309
LID - 10.1097/CM9.0000000000001463 [doi]
AB  - BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National 
      Medical Product Administration for the treatment of indolent B-cell non-Hodgkin 
      lymphoma (NHL). The current study was the registration trial and the first 
      reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine 
      in Chinese adult patients with indolent B-cell NHL following relapse after 
      chemotherapy and rituximab treatment. METHODS: This was a prospective, 
      multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) 
      with a 2-year follow-up period. Eligible patients received bendamustine 
      hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day 
      treatment cycle for at least six planned cycles (and up to eight cycles). The 
      primary endpoint was the overall response rate (ORR); and secondary endpoints 
      were duration of response (DoR), progression-free survival (PFS), safety, and 
      pharmacokinetics. Patients were classified according to their best overall 
      response after initiation of therapy. Proportions of patients in each response 
      category (complete response [CR], partial response [PR], stable disease, or 
      progressive disease) were summarized along with a two-sided binomial exact 95% 
      confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were 
      enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the 
      time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent 
      Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, 
      the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; 
      the median PFS was 18.6 months and 15.3 months, respectively. The most common 
      non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and 
      rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were 
      reported in 29 patients and five patients died during the study. Pharmacokinetic 
      analysis indicated that the characteristics of bendamustine and its metabolites 
      M3 and M4 were generally consistent with those reported for other ethnicities. 
      CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients 
      with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship 
      to that reported in North American patients. CLINICAL TRIAL REGISTRATION: 
      ClinicalTrials.gov, No. NCT01596621; 
      https://clinicaltrials.gov/ct2/show/NCT01596621.
CI  - Copyright (c) 2021 The Chinese Medical Association, produced by Wolters Kluwer, 
      Inc. under the CC-BY-NC-ND license.
FAU - Shi, Yuan-Kai
AU  - Shi YK
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking 
      Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer 
      Molecular Targeted Drugs, Beijing 100021, China.
FAU - Hong, Xiao-Nan
AU  - Hong XN
AD  - Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 
      200030, China.
FAU - Yang, Jian-Liang
AU  - Yang JL
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking 
      Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer 
      Molecular Targeted Drugs, Beijing 100021, China.
FAU - Xu, Wei
AU  - Xu W
AD  - Department of Hematology, The First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, Jiangsu 210029, China.
FAU - Huang, Hui-Qiang
AU  - Huang HQ
AD  - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 
      Guangdong 510060, China.
FAU - Xiao, Xiu-Bin
AU  - Xiao XB
AD  - Department of Medical Oncology, 307 Hospital of Chinese People's Liberation Army, 
      Beijing 100071, China.
FAU - Zhu, Jun
AU  - Zhu J
AD  - Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 
      100142, China.
FAU - Zhou, Dao-Bin
AU  - Zhou DB
AD  - Department of Hematology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
FAU - Han, Xiao-Hong
AU  - Han XH
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking 
      Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer 
      Molecular Targeted Drugs, Beijing 100021, China.
FAU - Wu, Jian-Qiu
AU  - Wu JQ
AD  - Department of Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer, 
      Nanjing, Jiangsu 210009, China.
FAU - Zhang, Ming-Zhi
AU  - Zhang MZ
AD  - Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan 450052, China.
FAU - Jin, Jie
AU  - Jin J
AD  - Department of Hematology, The First Affiliated Hospital of Zhejiang University 
      College of Medicine, Hangzhou, Zhejiang 310003, China.
FAU - Ke, Xiao-Yan
AU  - Ke XY
AD  - Department of Hematology, Peking University Third Hospital, Beijing 100191, 
      China.
FAU - Li, Wei
AU  - Li W
AD  - Department of Oncology, Jilin University First Affiliated Hospital, Changchun, 
      Jilin 130021, China.
FAU - Wu, De-Pei
AU  - Wu DP
AD  - Department of Hematology, Jiangsu Institute of Hematology, The First Affiliated 
      Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
FAU - Yang, Shen-Miao
AU  - Yang SM
AD  - Department of Hematology, Peking University Institute of Hematology, Peking 
      University People's Hospital, Beijing 100044, China.
FAU - Du, Xin
AU  - Du X
AD  - Department of Hematology, Guangdong General Hospital, Guangzhou, Guangdong 
      510062, China.
FAU - Jia, Yong-Qian
AU  - Jia YQ
AD  - Department of Hematology and Research Laboratory of Hematology, West China 
      Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
FAU - Liu, Ai-Chun
AU  - Liu AC
AD  - Department of Medical Oncology, Harbin Medical University Cancer Hospital, 
      Harbin, Heilongjiang 150001, China.
FAU - Liu, Dai-Hong
AU  - Liu DH
AD  - Department of Hematology, Chinese PLA General Hospital, Beijing 100038, China.
FAU - Shen, Zhi-Xiang
AU  - Shen ZX
AD  - Department of Hematology, Shanghai Ruijin Hospital, Shanghai 200020, China.
FAU - Zhang, Lian-Sheng
AU  - Zhang LS
AD  - Department of Hematology, The Second Hospital of Lanzhou University, Lanzhou, 
      Gansu 730030, China.
FAU - James, Leonard
AU  - James L
AD  - Department of Drug Metabolism and Pharmacokinetics, Teva Branded Pharmaceutical 
      Products R&D Inc., West Chester, PA 19380, USA.
FAU - Hellriegel, Edward
AU  - Hellriegel E
AD  - Department of Drug Metabolism and Pharmacokinetics, Teva Branded Pharmaceutical 
      Products R&D Inc., West Chester, PA 19380, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01596621
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
DEP - 20210506
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 981Y8SX18M (Bendamustine Hydrochloride)
SB  - IM
MH  - Adult
MH  - Antineoplastic Combined Chemotherapy Protocols
MH  - Bendamustine Hydrochloride/therapeutic use
MH  - China
MH  - Humans
MH  - *Lymphoma, Non-Hodgkin/drug therapy
MH  - *Neoplasm Recurrence, Local/drug therapy
MH  - Prospective Studies
MH  - Rituximab/therapeutic use
PMC - PMC8183773
COIS- Teva employees were involved in the study design, data collection and analysis, 
      and in the writing of this manuscript. All authors had full access to all the 
      study data and had final responsibility for the decision to submit for 
      publication. Leonard James and Edward Hellriegel are former employees of Teva 
      Pharmaceuticals.
EDAT- 2021/05/11 06:00
MHDA- 2021/06/04 06:00
PMCR- 2021/06/05
CRDT- 2021/05/10 06:12
PHST- 2021/05/11 06:00 [pubmed]
PHST- 2021/06/04 06:00 [medline]
PHST- 2021/05/10 06:12 [entrez]
PHST- 2021/06/05 00:00 [pmc-release]
AID - 00029330-202106050-00007 [pii]
AID - CMJ-2020-1915 [pii]
AID - 10.1097/CM9.0000000000001463 [doi]
PST - epublish
SO  - Chin Med J (Engl). 2021 May 6;134(11):1299-1309. doi: 
      10.1097/CM9.0000000000001463.