Circularly permuted TRAIL plus thalidomide and dexamethasone versus thalidomide and dexamethasone for relapsed/refractory multiple myeloma: a phase 2 study
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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).
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.
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.
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.
KeywordsRecombinant human circularly permuted TRAIL Multiple myeloma Thalidomide Dexamethasone Phase 2 clinical trials
The authors would like to thank all the patients and their families who contributed to the present study. The authors would like to thank all the staff members from the participating study sites.
Wenming Chen, Jian Hou, Shifang Yang and Xiangjun Zheng conceived, designed and performed the study; Yun Leng, Jian Hou, Jie Jin, Mei Zhang, Xiaoyan Ke, Bin Jiang, Ling Pan, Linhua Yang, Fang Zhou, Jianmin Wang, Zhao Wang, Li Liu, Wei Li, Zhixiang Shen, Lugui Qiu, Naibai Chang, Jianyong Li, Jing Liu, Haitao Meng, Hua Jiang, Yan Liu and Wenming Chen enrolled patients and collected data; Wenming Chen, Jian Hou, Shifang Yang, Xiangjun Zheng, Peng Wei and Hongyan Pang analyzed and interpreted the data; and all authors critically reviewed the manuscript for important intellectual content and approved the final draft.
Compliance with ethical standards
Conflict of interest
Beijing Sunbio Biotech Co. Ltd sponsored this clinical study and was responsible for medical monitoring and auditing. Shifang Yang, Xiangjun Zheng, Peng Wei and Hongyan Pang are employees of Beijing Sunbio Biotech Co., Ltd. All of the other authors declare no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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