Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial)

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 118; no. 6; pp. 1 - 10
• Main Authors: Chen, Li, Zhu, Hong-Ming, Li, Yan, Liu, Qi-Fa, Hu, Yu, Zhou, Jian-Feng, Jin, Jie, Hu, Jian-Da, Liu, Ting, Wu, De-Pei, Chen, Jie-Ping, Lai, Yong-Rong, Wang, Jian-Xiang, Li, Juan, Li, Jian-Yong, Du, Xin, Wang, Xin, Yang, Ming-Zhen, Yan, Jin-Song, Ouyang, Gui-Fang, Liu, Li, Hou, Ming, Huang, Xiao-Jun, Yan, Xiao-Jing, Xu, Dan, Li, Wei-Ming, Li, Deng-Ju, Lou, Yin-Jun, Wu, Zheng-Jun, Niu, Ting, Wang, Ying, Li, Xiao-Yang, You, Jian-Hua, Zhao, Hui-Jin, Chen, Yu, Shen, Yang, Chen, Qiu-Sheng, Li, Jian, Wang, Bing-Shun, Zhao, Wei-Li, Qing Mi, Jian, Wang, Kan-Kan, Hu, Jiong, Chen, Zhu, Chen, Sai-Juan, Li, Jun-Min
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 09.02.2021
• Subjects: Acute promyeloid leukemia; Anthracycline; Arsenic; Arsenic trioxide; Biological Sciences; Chemotherapy; Consolidation; Cytarabine; Evaluation; Induction therapy; Leukemia; Promyeloid leukemia; Remission; Retinoic acid; Risk groups; Toxicity; all-trans retinoic acid; acute promyelocytic leukemia; risk stratification; arsenic trioxide; consolidation therapy
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2020382118

As 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).