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 (CEBPAdm) 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 CEBPAdm AML.

Methods

This prospective multicenter single-arm trial enrolled patients with newly diagnosed CEBPAdm 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 CEBPAdm 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 CEBPAdm 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