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Circularly permuted TRAIL plus thalidomide and dexamethasone versus thalidomide and dexamethasone for relapsed/refractory multiple myeloma: a phase 2 study

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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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

    Yun Leng & Wenming Chen

  2. Department of Hematology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China

    Jian Hou & Hua Jiang

  3. Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

    Jie Jin & Haitao Meng

  4. Department of Hematology, The First Hospital of Xi’an Jiaotong University, Xi’an, Shanxi, China

    Mei Zhang

  5. Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, China

    Xiaoyan Ke & Yan Liu

  6. Department of Hematology, Peking University People’s Hospital, Beijing, China

    Bin Jiang

  7. Department of Hemotology, West China Hospital of Sichuan University, Chengdu, Sichuan, China

    Ling Pan

  8. Department of Hemotology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China

    Linhua Yang

  9. Department of Hematology, Jinan Military General Hospital, Jinan, Shandong, China

    Fang Zhou

  10. Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China

    Jianmin Wang

  11. Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China

    Zhao Wang

  12. Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shanxi, China

    Li Liu

  13. Department of Hematology, The First Hospital of Jilin University, Changchun, Jilin, China

    Wei Li

  14. Department of Hematology, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China

    Zhixiang Shen

  15. Department of Lymphoma Center, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin, China

    Lugui Qiu

  16. Department of Hematology, Beijing Hospital of the Ministry of Health, Beijing, China

    Naibai Chang

  17. Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

    Jianyong Li

  18. Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

    Jing Liu

  19. Beijing Sunbio Biotech Co. Ltd., Beijing, China

    Hongyan Pang, Peng Wei, Xiangjun Zheng & Shifang Yang

Authors
  1. Yun Leng
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  2. Jian Hou
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  3. Jie Jin
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  4. Mei Zhang
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  5. Xiaoyan Ke
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  6. Bin Jiang
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  7. Ling Pan
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  8. Linhua Yang
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  9. Fang Zhou
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  10. Jianmin Wang
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  11. Zhao Wang
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  12. Li Liu
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  13. Wei Li
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  14. Zhixiang Shen
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  15. Lugui Qiu
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  16. Naibai Chang
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  17. Jianyong Li
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  18. Jing Liu
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  19. Hongyan Pang
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  20. Haitao Meng
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  21. Peng Wei
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  22. Hua Jiang
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  23. Yan Liu
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  24. Xiangjun Zheng
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  25. Shifang Yang
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  26. Wenming Chen
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Contributions

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.

Corresponding author

Correspondence to Wenming Chen.

Ethics declarations

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.

Ethical approval

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

Informed consent was obtained from all individual participants included in the study.

Additional information

This trial was registered at http://www.chictr.org as ChiCTR-TRC-11001625.

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Leng, Y., Hou, J., Jin, J. et al. Circularly permuted TRAIL plus thalidomide and dexamethasone versus thalidomide and dexamethasone for relapsed/refractory multiple myeloma: a phase 2 study. Cancer Chemother Pharmacol 79, 1141–1149 (2017). https://doi.org/10.1007/s00280-017-3310-0

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  • DOI: https://doi.org/10.1007/s00280-017-3310-0

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