Homoharringtonine Combining with Azacitidine and Venetoclax (HAV) As First-Line Induction Therapy for Newly Diagnosed Adult Acute Myeloid Leukemia Patients

The targeted therapy regimen of venetoclax combined with demethylating agents has demonstrated a complete remission (CR) rate of approximately 70% in elderly or unfit patients with newly diagnosed acute myeloid leukemia (AML). However, its efficacy in newly diagnosed fit AML patients has been unsatisfactory, leading to a lack of recommendation for this cohort. Recent reports suggest that combining venetoclax with homoharringtonine enhances its anti-leukemic effects, with promising results observed in refractory/relapsed AML cases. This study aims to evaluate the safety and efficacy of the homoharringtonine, azacitidine, and venetoclax (HAV) regimen in treating newly diagnosed adult AML.

This retrospective study analyzed newly diagnosed AML patients who received induction therapy with the HAV regimen at Henan Provincial People's Hospital from January 2021 to December 2023. The HAV regimen comprised homoharringtonine (2 mg/d, days 1-7), azacitidine (75 mg/m²/d, days 1-7), and venetoclax (100 mg on day 1, 200 mg on day 2, 400 mg on days 3-14). The primary endpoint was the composite complete remission rate (cCR) after one cycle of induction therapy (CR+CRi). Secondary endpoints included event-free survival (EFS), overall survival (OS), and adverse effects.

A total of 24 newly diagnosed adult AML patients were included, with a median age of 62 years (range: 28-82 years). According to the 2022 ELN risk stratification, 3 patients were classified as favorable, 11 as intermediate, and 10 as adverse-risk. After one cycle of induction with the HAV regimen, the cCR rate was 95.8%, and the MRD-negative CR rate was 62.5%. Safety analysis revealed that grade ≥3 adverse reactions included neutropenia in 23 patients (95.8%), thrombocytopenia in 22 patients (91.7%), anemia in 11 patients (45.8%), febrile neutropenia in 23 patients (95.8%), and pneumonia in 7 patients (29.2%). No treatment-related deaths occurred. The median follow-up time was 221 days, with a 1-year OS rate of 90% (95% CI: 76.9%-100%) and a 1-year EFS rate of 72.4% (95% CI: 51.6%-93.2%).

In conclusion, the HAV regimen is an effective and safe induction therapy for newly diagnosed AML patients, achieving a high complete remission rate. This regimen offers a promising treatment strategy for adult patients with newly diagnosed AML.

No relevant conflicts of interest to declare.