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Open Access 01-12-2023 | Multiple Myeloma | Research

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial

Authors: Zhongjun Xia, Yun Leng, Baijun Fang, Yang Liang, Wei Li, Chengcheng Fu, Linhua Yang, Xiaoyan Ke, Hua Jiang, Jianyu Weng, Li Liu, Yaozhong Zhao, Xuejun Zhang, Zhongxia Huang, Aichun Liu, Qingzhi Shi, Yuhuan Gao, Xiequn Chen, Ling Pan, Zhen Cai, Zhao Wang, Yafei Wang, Yaqun Fan, Ming Hou, Yigai Ma, Jianda Hu, Jing Liu, Jianfeng Zhou, Xiaohong Zhang, Haitao Meng, Xuzhang Lu, Fei Li, Hanyun Ren, Bintao Huang, Zonghong Shao, Hebing Zhou, Yu Hu, Shifang Yang, Xiangjun Zheng, Peng Wei, Hongyan Pang, Wei Yu, Yuzhang Liu, Sujun Gao, Lingzhi Yan, Yanping Ma, Hongmei Jing, Juan Du, Wei Ling, Jingyi Zhang, Weiwei Sui, Fuxu Wang, Xin Li, Wenming Chen

Published in: BMC Cancer | Issue 1/2023

Abstract

Background

Aponermin, a circularly permuted tumor necrosis factor-related apoptosis-inducing ligand, is a potential death receptor 4/5-targeted antitumour candidate. Previous phase 1/2 studies have demonstrated the efficacy of aponermin in patients with relapsed or refractory multiple myeloma (RRMM). To confirm the superiority of aponermin plus thalidomide and dexamethasone (aponermin group) over placebo plus thalidomide and dexamethasone (placebo group) in RRMM, a randomized, double-blinded, placebo controlled phase 3 trial was performed.

Methods

Four hundred seventeen patients with RRMM who had previously received at least two regimens were randomly assigned (2:1) to receive aponermin, thalidomide, and dexamethasone or placebo, thalidomide, and dexamethasone. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and overall response rate (ORR).

Results

A total of 415 patients received at least one dose of trial treatment (276 vs. 139). The median PFS was 5.5 months in the aponermin group and 3.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.49–0.78; P < 0.001). The median OS was 22.4 months for the aponermin group and 16.4 months for the placebo group (hazard ratio, 0.70; 95% CI, 0.55–0.89; P = 0.003). Significantly higher rates of ORR (30.4% vs. 13.7%, P < 0.001) and very good partial response or better (14.1% vs. 2.2%, P < 0.0001) were achieved in the aponermin group than in the placebo group. Treatment with aponermin caused hepatotoxicity in some patients, as indicated by the elevated alanine transaminase, aspartate transaminase, or lactate dehydrogenase levels (52.2% vs. 24.5%, 51.1% vs. 19.4% and 44.9% vs. 21.6%, respectively), mostly grade 1/2, transient and reversible. The main grade 3/4 adverse events included neutropenia, pneumonia and hyperglycemia. The incidence of serious adverse events was similar between the two groups (40.6% vs. 37.4%). There was no evidence that aponermin leads to hematological toxicity, nephrotoxicity, cardiotoxicity, or secondary tumors.

Conclusions

Aponermin plus thalidomide and dexamethasone significantly improved PFS, OS and ORR with manageable side effects in RRMM patients who had received at least two prior therapies. These results support the use of aponermin, thalidomide, and dexamethasone as a treatment option for RRMM patients.

Trial registration

The trial was registered at http://www.chictr.org.cn as ChiCTR-IPR-15006024, 17/11/2014.

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Title: Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial
Authors: Zhongjun Xia
Yun Leng
Baijun Fang
Yang Liang
Wei Li
Chengcheng Fu
Linhua Yang
Xiaoyan Ke
Hua Jiang
Jianyu Weng
Li Liu
Yaozhong Zhao
Xuejun Zhang
Zhongxia Huang
Aichun Liu
Qingzhi Shi
Yuhuan Gao
Xiequn Chen
Ling Pan
Zhen Cai
Zhao Wang
Yafei Wang
Yaqun Fan
Ming Hou
Yigai Ma
Jianda Hu
Jing Liu
Jianfeng Zhou
Xiaohong Zhang
Haitao Meng
Xuzhang Lu
Fei Li
Hanyun Ren
Bintao Huang
Zonghong Shao
Hebing Zhou
Yu Hu
Shifang Yang
Xiangjun Zheng
Peng Wei
Hongyan Pang
Wei Yu
Yuzhang Liu
Sujun Gao
Lingzhi Yan
Yanping Ma
Hongmei Jing
Juan Du
Wei Ling
Jingyi Zhang
Weiwei Sui
Fuxu Wang
Xin Li
Wenming Chen
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Multiple Myeloma
Published in: BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-023-11489-8

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