• 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, and Jun-Min Li.
• Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China.
• Proc. Natl. Acad. Sci. U.S.A. 2021 Feb 9; 118 (6).

AbstractAs all-trans 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 (P < 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 (P = 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], P = 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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