Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes

作者全名：Tian, Jie; Song, Yong-Ping; Zhang, Gao-Chong; Wang, Shu-Fang; Chu, Xiao-Xiang; Chai, Ye; Wang, Chun-Ling; He, Ai-Li; Zhang, Feng; Shen, Xu-Liang; Zhang, Wei-Hua; Yang, Lin-Hua; Nie, Da-Nian; Wang, Dong-Mei; Zhu, Huan-Ling; Gao, Da; Lou, Shi-Feng; Zhou, Ze-Ping; Su, Guo-Hong; Li, Yan; Lin, Jin-Ying; Shi, Qing-Zhi; Ouyang, Gui-Fang; Jing, Hong-Mei; Chen, Sai-Juan; Li, Jian; Mi, Jian-Qing

作者地址：[Tian, Jie; Chen, Sai-Juan; Li, Jian; Mi, Jian-Qing] Shanghai Jiao Tong Univ, Shanghai Inst Hematol, Natl Res Ctr Translat Med Shanghai, State Key Lab Med Genom,Ruijin Hosp,Sch Med, Shanghai, Peoples R China; [Song, Yong-Ping] Zhengzhou Univ, Affiliated Canc Hosp, Zhengzhou, Henan, Peoples R China; [Zhang, Gao-Chong; Wang, Shu-Fang; Chu, Xiao-Xiang] Yifan Res & Dev, Hefei, Anhui, Peoples R China; [Chai, Ye] Lanzhou Univ, Hosp 2, Lanzhou, Gansu, Peoples R China; [Wang, Chun-Ling] Nanjing Med Univ, Affiliated Huaian 1 Peoples Hosp, Huaian, Jiangsu, Peoples R China; [He, Ai-Li] Xi An Jiao Tong Univ, Affiliated Hosp 2, Xian, Shaanxi, Peoples R China; [Zhang, Feng] Bengbu Med Coll, Affiliated Hosp 1, Bengbu, Anhui, Peoples R China; [Shen, Xu-Liang] Heping Hosp, Changzhi Med Coll, Changzhi, Shanxi, Peoples R China; [Zhang, Wei-Hua] Shanxi Med Univ, Hosp 1, Taiyuan, Shanxi, Peoples R China; [Yang, Lin-Hua] Shanxi Med Univ, Hosp 2, Taiyuan, Shanxi, Peoples R China; [Nie, Da-Nian] Sun Yat Sen Univ, Affiliated Hosp 2, Guangzhou, Guangdong, Peoples R China; [Wang, Dong-Mei] Hengshui Peoples Hosp, Hengshui, Hebei, Peoples R China; [Zhu, Huan-Ling] Sichuan Univ, West China Hosp, Chengdu, Sichuan, Peoples R China; [Gao, Da] Inner Mongolia Med Univ, Affiliated Hosp, Hohhot, Inner Mongolia, Peoples R China; [Lou, Shi-Feng] Chongqing Med Univ, Affiliated Hosp 2, Chongqing, Peoples R China; [Zhou, Ze-Ping] Kunming Med Univ, Affiliated Hosp 2, Kunming, Yunnan, Peoples R China; [Su, Guo-Hong] Cangzhou Cent Hosp, Cangzhou, Hebei, Peoples R China; [Li, Yan] China Med Univ, Affiliated Hosp 1, Shenyang, Liaoning, Peoples R China; [Lin, Jin-Ying] Peoples Hosp Guangxi Zhuang Autonomous Reg, Nanning, Guangxi Zhuang, Peoples R China; [Shi, Qing-Zhi] Nanchang Univ, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China; [Ouyang, Gui-Fang] Ningbo First Hosp, Ningbo, Zhejiang, Peoples R China; [Jing, Hong-Mei] Peking Univ Third Hosp, Beijing, Peoples R China

通信作者：Chen, SJ; Li, J; Mi, JQ (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Inst Hematol, Natl Res Ctr Translat Med Shanghai, State Key Lab Med Genom,Ruijin Hosp,Sch Med, Shanghai, Peoples R China.

来源：JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001200427200002

JCR分区：Q3

影响因子：2.7

年份：2024

卷号：150

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：Chronic myeloid leukemia; Arsenic; Imatinib; Efficacy and safety

摘要：Purpose The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML).Methods In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events.Results The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups.Conclusion The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

基金机构：Yifan Pharmaceutical Co., Ltd.

基金资助正文：This study was sponsored by Yifan Pharmaceutical Co., Ltd.