Homoharringtonine-Based Induction Regimen Improved the Remission Rate and Survival Rate in Chinese Childhood AML: A Report From the CCLG-AML 2015 Protocol Study.

Jing Li ,Xiaodong Shi ,Min Zhou ,Qun Hu ,Lian-Yue Yang ,Mei Yan ,Jing Wang ,Weihong Zhao ,Peijing Qi ,Xiaowen Zhai ,Liting Xu ,Leping Zhang ,Chen‐Hua Yan ,Pengli Huang ,Ying Wu ,Wei Liu ,Jingbo Shao ,Chaozhao Liang ,Xiaoli Wang ,Yuanyuan Zhang ,Chao Gao ,Li Wang ,Li‐Min Lin ,Hao Xiong ,Rong Zhang ,Ansheng Liu ,Yilin Wang ,Yongjun Fang ,Win Lin ,Sen Chen ,Xin Tian ,Junlan Wang ,Jia Fan ,Rui‐Dong Zhang ,Ju Gao ,Yunpeng Dai ,Jin Jian ,Lingzhen Wang ,Cao H ,Yaguang Peng ,Xiaoxia Peng ,Yueqin Han ,Xiuli Ju ,Hui Liang ,Jiaole Yu ,Hui Yu ,Jingrong Zhang ,Tianyou Wang ,Huyong Zheng

doi:10.1200/jco.22.02836

Abstract

Homoharringtonine (HHT) is commonly used for the treatment of Chinese adult AML, and all-trans retinoic acid (ATRA) has been verified in acute promyelocytic leukemia (APL). However, the efficacy and safety of HHT-based induction therapy have not been confirmed for childhood AML, and ATRA-based treatment has not been evaluated among patients with non-APL AML. This open-label, multicenter, randomized Chinese Children's Leukemia Group-AML 2015 study was performed across 35 centers in China. Patients with newly diagnosed childhood AML were first randomly assigned to receive an HHT-based (H arm) or etoposide-based (E arm) induction regimen and then randomly allocated to receive cytarabine-based (AC arm) or ATRA-based (AT arm) maintenance therapy. The primary end points were the complete remission (CR) rate after induction therapy, and the secondary end points were the overall survival (OS) and event-free survival (EFS) at 3 years. We enrolled 1,258 patients, of whom 1,253 were included in the intent-to-treat analysis. The overall CR rate was significantly higher in the H arm than in the E arm (79.9% v 73.9%, P = .014). According to the intention-to-treat analysis, the 3-year OS was 69.2% (95% CI, 65.1 to 72.9) in the H arm and 62.8% (95% CI, 58.7 to 66.6) in the E arm (P = .025); the 3-year EFS was 61.1% (95% CI, 56.8 to 65.0) in the H arm and 53.4% (95% CI, 49.2 to 57.3) in the E arm (P = .022). Among the per-protocol population, who received maintenance therapy, the 3-year EFS did not differ significantly across the four arms (H + AT arm: 70.7%, 95% CI, 61.1 to 78.3; H + AC arm: 74.8%, 95% CI, 67.0 to 81.0, P = .933; E + AC arm: 72.9%, 95% CI, 65.1 to 79.2, P = .789; E + AT arm: 66.2%, 95% CI, 56.8 to 74.0, P = .336). HHT is an alternative combination regimen for childhood AML. The effects of ATRA-based maintenance are comparable with those of cytarabine-based maintenance therapy.

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