KEY TAKEAWAYS
- The phase 3 trial aimed to compare arsenic RIF plus imatinib with imatinib alone in patients with newly diagnosed CP-CML.
- The primary endpoint was MMR.
- Imatinib plus RIF as initial CP-CML therapy may achieve a deeper molecular response than imatinib alone.
In vitro data confirms the synergistic potential of arsenic compounds combined with imatinib against chronic myeloid leukemia (CML).
Jie Tian and the team aimed to assess the efficacy of arsenic realgar-indigo naturalis formula (RIF) plus imatinib versus imatinib alone in newly diagnosed chronic phase CML (CP-CML) patients through a clinical trial.
This double-blind, multicenter, randomized phase 3 trial involved 191 newly diagnosed CP-CML outpatients. They were randomly allocated to receive either oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95).
The primary endpoint was achieving major molecular response (MMR) at 6 months. Secondary endpoints included molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events (AEs).
The median follow-up lasted 51 months, with recruitment concluding prematurely on May 28, 2020, due to the COVID-19 pandemic. At 6 months and throughout the trial, there was no significant difference in MMR rates between the combination and imatinib arms. Rates of molecular response 4 (MR4) were comparable between both arms.
However, the 12-month cumulative rates of molecular response 4.5 (MR4.5) were 20.8% and 10.5% in the combination and imatinib arms, respectively (P= 0.043).
In the core treatment phase post-2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (P= 0.063). PFS and OS were comparable at 5 years. Safety profiles were similar, with both groups’ rare occurrence of serious AEs.
The analysis showed that combining imatinib with RIF as initial CP-CML therapy might enhance the achievement of a deeper molecular response compared to imatinib alone.
Funding was received by the Yifan Pharmaceutical Co., Ltd.
Source: https://pubmed.ncbi.nlm.nih.gov/38605258/
Clinical Trial: http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml
Tian J, Song YP, Zhang GC, et al. (2024) “Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.” J Cancer Res Clin Oncol. 2024 Apr 11;150(4):189. doi: 10.1007/s00432-024-05700-x. PMID: 38605258; PMCID: PMC11009770.
