Li Chen, Hong-Ming Zhu, Yan Li, Qi-Fa Liu, Yu Hu, Jian-Feng Zhou, Jie Jin, Jian-Da Hu, Ting Liu, De-Pei Wu, Jie-Ping Chen, Yong-Rong Lai, Jian-Xiang Wang, Juan Li, Jian-Yong Li, Xin Du, Xin Wang, Ming-Zhen Yang, Jin-Song Yan, Gui-Fang Ouyang, Li Liu, Ming Hou, Xiao-Jun Huang, Xiao-Jing Yan, Dan Xu, Wei-Ming Li, Deng-Ju Li, Yin-Jun Lou, Zheng-Jun Wu, Ting Niu, Ying Wang, Xiao-Yang Li, Jian-Hua You, Hui-Jin Zhao, Yú Chen, Yang Shen, Qiu-Sheng Chen, Yù Chen, Jian Li, Bing-Shun Wang, Wei-Li Zhao, Jian-Qing Mi, Kan-Kan Wang, Jiong Hu, Zhu Chen, Sai-Juan Chen, Jun-Min Li
Journal: Proceedings of the National Academy of Sciences of the United States of America 2021;118(6):e2020382118
PMID: 33495363
As all- retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority ( < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups ( = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).
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