Phase II open-label study of recombinant circularly permuted TRAIL as a single-agent treatment for relapsed or refractory multiple myeloma.
Despite the recent development of new therapies, multiple myeloma (MM) remains an incurable disease. Thus, new, effective 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 efficacy and safety of 2.5-mg/kg per day CPT as single-agent therapy for patients with RRMM.



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.



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 (nCR) and 8 partial responses (PRs). The clinical benefit rate (48.1%) included 1 nCR, 8 PRs, and 4 minimal responses. The most common treatment-related 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.



CPT as a single agent can elicit a response in patients with RRMM and is well tolerated. Further clinical investigation is warranted. Trial Registration ChiCTR-ONC-12002065 http://www.chictr.org/cn.
Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, P. R. China.
Yun
Y
Leng
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.
Lugui
L
Qiu
Department of Hematology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, P. R. China.
Jian
J
Hou
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.
Yaozhong
Y
Zhao
Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, P. R. China.
Xuejun
X
Zhang
Beijing Sunbio Biotech Co., Ltd., Beijing, 100176, P. R. China.
Shifang
S
Yang
Department of Hematology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, P. R. China.
Hao
H
Xi
Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, P. R. China.
Zhongxia
Z
Huang
Department of Hematology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, P. R. China.
Ling
L
Pan
Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, P. R. China. xybxx@ccmu.edu.cn.
Wenming
W
Chen
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use*; D016879:Salvage Therapy; D015996:Survival Rate; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human
Efficacy; Phase II trial; Recombinant human circularly permuted TRAIL; Relapsed or refractory multiple myeloma; Safety