Yun Leng1, Jian Hou2, Jie Jin3, Mei Zhang4, Xiaoyan Ke5, Bin Jiang6, Ling Pan7, Linhua Yang8, Fang Zhou9, Jianmin Wang10, Zhao Wang11, Li Liu12, Wei Li13, Zhixiang Shen14, Lugui Qiu15, Naibai Chang16, Jianyong Li17, Jing Liu18, Hongyan Pang19, Haitao Meng3, Peng Wei19, Hua Jiang2, Yan Liu5, Xiangjun Zheng19, Shifang Yang19, Wenming Chen20. 1. Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. 2. Department of Hematology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China. 3. Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 4. Department of Hematology, The First Hospital of Xi'an Jiaotong University, Xi'an, Shanxi, China. 5. Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, China. 6. Department of Hematology, Peking University People's Hospital, Beijing, China. 7. Department of Hemotology, West China Hospital of Sichuan University, Chengdu, Sichuan, China. 8. Department of Hemotology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. 9. Department of Hematology, Jinan Military General Hospital, Jinan, Shandong, China. 10. Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China. 11. Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China. 12. Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi, China. 13. Department of Hematology, The First Hospital of Jilin University, Changchun, Jilin, China. 14. Department of Hematology, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China. 15. Department of Lymphoma Center, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin, China. 16. Department of Hematology, Beijing Hospital of the Ministry of Health, Beijing, China. 17. Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. 18. Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China. 19. Beijing Sunbio Biotech Co. Ltd., Beijing, China. 20. Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. xybxx@ccmu.edu.cn.
Abstract
PURPOSE:Circularly permuted TRAIL (CPT) has exhibited promising efficacy as a mono-therapy or in combination with thalidomide for patients with multiple myeloma (MM). In this phase 2 study, the safety and efficacy of CPT in combination with thalidomide and dexamethasone (CPT + TD) was evaluated in patients with pretreated relapsed/refractory MM (RRMM). METHODS:Patients who received at least two previous therapies for MM were randomly assigned at a 2:1 ratio to receive treatment with CPT + TD or thalidomide and dexamethasone (TD). The primary endpoint was the overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), duration of response (DOR) and safety. RESULTS: Overall, 47 patients were assigned to the CPT + TD group, and 24 patients were recruited to the TD group. The ORR in the CPT + TD group was 38.3 vs. 25.0% in the TD group. The median PFS time was 6.7 months for the CPT + TD group and 3.1 months for the TD group. The median DORs for the CPT + TD and TD groups were 7.1 and 3.2 months, respectively. Most of the adverse effects (AEs) were grade 1 or 2. Serious AEs were reported in 19.7% of the patients. No treatment-related deaths were reported. CONCLUSION:CPT plus TD could serve as a new therapeutic strategy for patients with RRMM. A randomized, double-blind, placebo-controlled confirmatory study is currently under way.
RCT Entities:
PURPOSE: Circularly permuted TRAIL (CPT) has exhibited promising efficacy as a mono-therapy or in combination with thalidomide for patients with multiple myeloma (MM). In this phase 2 study, the safety and efficacy of CPT in combination with thalidomide and dexamethasone (CPT + TD) was evaluated in patients with pretreated relapsed/refractory MM (RRMM). METHODS:Patients who received at least two previous therapies for MM were randomly assigned at a 2:1 ratio to receive treatment with CPT + TD or thalidomide and dexamethasone (TD). The primary endpoint was the overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), duration of response (DOR) and safety. RESULTS: Overall, 47 patients were assigned to the CPT + TD group, and 24 patients were recruited to the TD group. The ORR in the CPT + TD group was 38.3 vs. 25.0% in the TD group. The median PFS time was 6.7 months for the CPT + TD group and 3.1 months for the TD group. The median DORs for the CPT + TD and TD groups were 7.1 and 3.2 months, respectively. Most of the adverse effects (AEs) were grade 1 or 2. Serious AEs were reported in 19.7% of the patients. No treatment-related deaths were reported. CONCLUSION: CPT plus TD could serve as a new therapeutic strategy for patients with RRMM. A randomized, double-blind, placebo-controlled confirmatory study is currently under way.
Authors: Mohammed I Y Elmallah; Sheron Cogo; Andrei A Constantinescu; Selene Elifio-Esposito; Mohammed S Abdelfattah; Olivier Micheau Journal: Cells Date: 2020-07-22 Impact factor: 6.600