Efficacy of homoharringtonine-based induction regimen in acute myeloid leukemia (AML) with double-mutated CCAAT/enhancer-binding protein alpha (CEBPA): A prospective multicenter, single-arm trial

Background Homoharringtonine (HHT) suppresses the expression of the CCAAT/enhancer-binding protein alpha (CEBPA). Our previous retrospective analysis indicated that favorable outcomes were observed in acute myeloid leukemia (AML) with double-mutated CEBPA ( CEBPA dm) when patients received an HHT-based induction regimen. To confirm these observations, we performed a prospective multicenter, single-arm trial to assess the efficacy of homoharringtonine, daunorubicin, and cytarabine (HAD) induction regimen in patients with CEBPA dm AML. Methods This prospective multicenter single-arm trial enrolled patients with newly diagnosed CEBPA dm AML who received the HAD induction regimen between June 1, 2020, and October 1, 2023. Consolidation therapy comprised three cycles of high-dose cytarabine (HDAC). The trial was registered at ClinicalTrials.gov (NCT04415008). The primary outcomes were event-free survival (EFS) and relapse-free survival (RFS). Secondary endpoints included complete remission (CR) rate, 30-day mortality, and overall survival (OS). Survival outcomes were estimated using the Kaplan-Meier method and compared with the log-rank test. Results A total of 61 patients with newly diagnosed CEBPA dm AML (median age 40 years, interquartile range [IQR] 30–47 years) were enrolled. After one course of HAD induction, 57 patients (93.44%) achieved complete remission (CR), and the overall CR rate after one or two courses reached 95.08% (58/61). Among the 58 responders, 46 patients (79.31% [46/58]) achieved measurable residual disease (MRD) negativity after the first induction. The 30-day mortality rate was 3.28% (2/61). At a median follow-up of 31.97 months (IQR 21.27–37.77), the estimated 3-year EFS, RFS, and OS rates were 77.86%, 82.16%, and 87.27%, respectively. Exploratory subgroup analyses showed a numerical trend toward inferior RFS in patients with the co-occurring colony stimulating factor 3 receptor ( CSF3R ) T618I mutation ( P = 0.064); however, given the small subgroup size, these findings are hypothesis-generating only and require validation in larger cohorts. Conclusions The HAD regimen demonstrated promising clinical activity and an acceptable safety profile in young adult patients with CEBPA dm AML, with 3-year EFS and RFS rates that met the predetermined objectives of 72% and 75%, respectively. Trial registration No. NCT04415008; https://classic.clinicaltrials.gov .