Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study.

Yuan-kai Shi; Xiao-nan Hong; Jian-liang Yang; Wei XU; Hui-qiang Huang; Xiu-bin Xiao; Jun Zhu; Dao-bin Zhou; Xiao-hong Han; Jian-qiu WU; Ming-zhi Zhang; Jie Jin; Xiao-yan KE; Wei LI; De-pei WU; Shen-miao Yang; Xin DU; Yong-qian Jia; Ai-chun Liu; Dai-hong Liu; Zhi-xiang Shen; Lian-sheng Zhang; Leonard James; Edward Hellriegel

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Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study.

Author: Yuan-Kai SHI ¹ ; Xiao-Nan HONG ² ; Jian-Liang YANG ¹ ; Wei XU ³ ; Hui-Qiang HUANG ⁴ ; Xiu-Bin XIAO ⁵ ; Jun ZHU ⁶ ; Dao-Bin ZHOU ⁷ ; Xiao-Hong HAN ¹ ; Jian-Qiu WU ⁸ ; Ming-Zhi ZHANG ⁹ ; Jie JIN ¹⁰ ; Xiao-Yan KE ¹¹ ; Wei LI ¹² ; De-Pei WU ¹³ ; Shen-Miao YANG ¹⁴ ; Xin DU ¹⁵ ; Yong-Qian JIA ¹⁶ ; Ai-Chun LIU ¹⁷ ; Dai-Hong LIU ¹⁸ ; Zhi-Xiang SHEN ¹⁹ ; Lian-Sheng ZHANG ²⁰ ; Leonard JAMES ²¹ ; Edward HELLRIEGEL ²¹
Author Information

1. 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.
2. Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200030, China.
3. Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
4. Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
5. Department of Medical Oncology, 307 Hospital of Chinese People's Liberation Army, Beijing 100071, China.
6. Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 100142, China.
7. Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
8. Department of Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer, Nanjing, Jiangsu 210009, China.
9. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
10. Department of Hematology, The First Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang 310003, China.
11. Department of Hematology, Peking University Third Hospital, Beijing 100191, China.
12. Department of Oncology, Jilin University First Affiliated Hospital, Changchun, Jilin 130021, China.
13. Department of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
14. Department of Hematology, Peking University Institute of Hematology, Peking University People's Hospital, Beijing 100044, China.
15. Department of Hematology, Guangdong General Hospital, Guangzhou, Guangdong 510062, China.
16. Department of Hematology and Research Laboratory of Hematology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
17. Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150001, China.
18. Department of Hematology, Chinese PLA General Hospital, Beijing 100038, China.
19. Department of Hematology, Shanghai Ruijin Hospital, Shanghai 200020, China.
20. Department of Hematology, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China.
21. Department of Drug Metabolism and Pharmacokinetics, Teva Branded Pharmaceutical Products R&D Inc., West Chester, PA 19380, USA.
Publication Type:Multicenter Study
MeSH: Adult; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride/therapeutic use*; China; Humans; Lymphoma, Non-Hodgkin/drug therapy*; Neoplasm Recurrence, Local/drug therapy*; Prospective Studies; Rituximab/therapeutic use*
From: Chinese Medical Journal 2021;134(11):1299-1309
CountryChina
Language:English
Abstract: 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.