Phase Ⅱ open-label study of recombinant circularly permuted TRAIL as a single-agent treatment for relapsed or refractory multiple myeloma

• Published in: Ai zheng Vol. 35; no. 12; pp. 699 - 705
• Main Authors: Leng, Yun, Qiu, Lugui, Hou, Jian, Zhao, Yaozhong, Zhang, Xuejun, Yang, Shifang, Xi, Hao, Huang, Zhongxia, Pan, Ling, Chen, Wenming
• Format: Journal Article
• Language: English
• Published: London BioMed Central 08.09.2016; BioMed Central Ltd; John Wiley & Sons, Inc; Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing 100020, P. R. China%Department of Lymphoma Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, P. R. China%Department of Hematology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai 200003, P. R. China%Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, P. R. China%Beijing Sunbio Biotech Co., Ltd., Beijing 100176, P. R. China%Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, P. R. China; BMC
• Subjects: Adult; Aged; Antineoplastic Agents - therapeutic use; Apoptosis; Aspartate; Clinical trials; Diseases; Drug Resistance, Neoplasm; Efficacy; Female; Follow-Up Studies; Humans; Labels; Male; Medical research; Medicine, Experimental; Middle Aged; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - pathology; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Original; Phase II trial; Prognosis; Recombinant human circularly permuted TRAIL; Recombinant Proteins - therapeutic use; Relapse; Relapsed or refractory multiple myeloma; Safety; Salvage Therapy; Survival Rate; TNF-Related Apoptosis-Inducing Ligand - therapeutic use; Efficacy; Safety; Recombinant human circularly permuted TRAIL; Relapsed or refractory multiple myeloma; Phase II trial; Effcacy
• ISSN: 1000-467X; 2523-3548; 1944-446X; 1944-446X; 2523-3548
• DOI: 10.1186/s40880-016-0140-0

Background： Despite the recent development of new therapies, multiple myeloma（MM） remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM（RRMM）. In an earlier phase I study, a novel form of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand（TRAIL） that is currently in clinical development for the treatment of hematologic malignancies, i.e., circularly permuted TRAIL（CPT）, was well tolerated at a dose of 2.5 mg/kg per day and showed promising preliminary activity in patients with RRMM. This phase II, open-label, multicenter study further investigated the eicacy and safety of 2.5-mg/kg per day CPT as single-agent therapy for patients with RRMM.Methods： Patients with RRMM were treated once daily with CPT（2.5 mg/kg, intravenously） for 14 consecutive days for each 21-day cycle. Clinical response and toxicity were assessed after each treatment cycle.Results： Twenty-seven patients received CPT. Using the European Group for Blood and Marrow Transplantation criteria, we calculated the overall response rate of 33.3% with 1 near-complete response（n CR） and 8 partial responses（PRs）. The clinical beneit rate（48.1%） included 1 nCR, 8 PRs, and 4 minimal responses. The most common treatmentrelated adverse events（TRAEs） were fever, aspartate aminotransferase elevation, alanine aminotransferase elevation, leucopenia, rash, neutropenia, and thrombocytopenia. We graded toxicity using the Common Toxicity Criteria for Adverse Events, version 3.0, and determined that 37.0% of patients had at least 1 grade 3–4 TRAE.Conclusions： CPT as a single agent can elicit a response in patients with RRMM and is well tolerated. Further clinical investigation is warranted.