Background: The survival rate of patients diagnosed with acute myeloid leukemia (AML) has shown improvement in recent decades. However, the induction chemotherapy regimen for AML still relies on the standard 7+3 regimen. Standard 7+3 regimen can achieve a complete response (CR) rate of 70%-80% in AML patients up to 60 years of age and 50% in older patients. After years of development, the CR rate has shown improvement in both young and elderly AML patients. However, more than 20%-30% of patients still fail to achieve a response after induction chemotherapy, particularly among elderly patients who are deemed unfit. Based on this premise, we endeavored to develop a low-dose, long-course CHG regimen (cytarabine, homoharringtonine, and granulocyte stimulating factor) in combination with the demethylating agent azacytidine and the Bcl-2 inhibitor venetoclax as an induction regimen(NCT06470841). Our aim is to investigate a more efficient and safer induction chemotherapy regimen.

Methods: Adult patients with AML were enrolled to receive VACHG induction chemotherapy treatment (venetoclax 100mg po qd d1, 200mg po qd d2, 400mg po qd d3-14; azacytidine 75 mg/m2 subcutaneous injection qd d1-7; homoharringtonine 1mg/m2 iv qd d1-14; cytarabine 10mg/m2 subcutaneous injection q12h d1-14; granulocyte stimulating factor 250ug/m2 subcutaneous injection qd d0-14). After induction therapy, patients will be given standardized treatment according to risk stratification according to NCCN guidelines (NCT06470841).

Results: We have currently enrolled a total of 5 patients with acute myeloid leukemia. Among them, 3 patients were over 65 years of age with newly diagnosed acute myeloid leukemia, while the remaining 2 patients were under 60 years of age with refractory/refractory acute myeloid leukemia. One patient achieved CRi after receiving daunorubicin plus cytarabine (DA) induction chemotherapy. However, the patient relapsed after completing 2 courses of consolidation chemotherapy (1 course of DA and 1 course of venetoclax + azacytidine + sorafenib). The patient then obtained CR after completing 1 course of VACHG reinduction chemotherapy. In another patient, non-response (NR) was observed after 1 course of idarubicin plus cytarabine. After the second course of venetoclax + azacytidine(VA) induction chemotherapy, the patient still achieved NR. Then, the patient underwent treatment with the VACHG regimen and achieved CR after a single course of induction chemotherapy using the VACHG regimen. Three additional elderly patients, who were newly diagnosed with AML, achieved a complete response after receiving a single course of VACHG chemotherapy. All the 2 refractory/relapsed AML patients and 3 newly diagnosed elderly AML patients achieved complete remission by a single course of VACHG induction chemotherapy. Grade Ⅳ myelosuppression and infection were observed in all five patients. Two patients experienced gastrointestinal hemorrhage, while one patient suffered from acute kidney injury. Side effects were effectively managed. Following the achievement of complete response, the two refractory/relapsed patients underwent allogeneic hematopoietic stem cell transplantation. The three elderly patients received consolidation and maintenance therapy after achieving complete response.

Conclusion: In this trial, we utilized a low-dose, long-course regimen of CHG in combination with the demethylating drug azacytidine and the Bcl-2 inhibitor venetoclax as an induction regimen. Notably, all 5 patients achieved complete remission by a single course of VACHG induction chemotherapy, and the combined chemotherapy regimen demonstrated excellent tolerance in both young and elderly patients. This combined chemotherapy regimen demonstrated remarkable efficacy and merits further implementation. Further enrollment of more patients is necessary to better clarify the effectiveness and safety of VACHG regimen as induction chemotherapy in AML patients.

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2025
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