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

• Published in: Journal of cancer research and clinical oncology Vol. 150; no. 4; p. 189
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 11-04-2024; Springer Nature B.V
• Subjects: Adverse events; Arsenic; Cancer Research; Chronic myeloid leukemia; Clinical trials; COVID-19; Hematology; Imatinib; Indigo; Internal Medicine; Leukemia; Medicine; Medicine & Public Health; Myeloid leukemia; Oncology; Statistical analysis; Survival; Imatinib; Chronic myeloid leukemia; Efficacy and safety; Arsenic
• ISSN: 1432-1335; 0171-5216; 1432-1335
• DOI: 10.1007/s00432-024-05700-x

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 (MR
4
), molecular response 4.5 (MR
4.5
), 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. MR
4
rates were similar in both arms. However, the 12-month cumulative rates of MR
4.5
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 MR
4.5
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).