Background: Venetoclax plus azacitidine (VA regimen) is recommended for treatment-naive patients with acute myeloid leukaemia (AML) who are unfit for intensive chemotherapy. However, the composite complete remission rate after one cycle of VA regimen is only 43.4%, which need to be improved. Regimens containing granulocyte colony-stimulating factor (G-CSF), such as FLAG,CLAG, CAG and HAG have been used in clinical practice for many years and has shown certain efficacy. We presumed that venetoclax plus azacitidine in combination with G-CSF (referred to as the VAG regimen) could have a better composite complete remission rate while maintaining an acceptable safety profile.

Methods: All patients received induction with venetoclax (100mg d1, 200mg d2, 400 mg d3-14, orally), azacitidine (100 mg/d, d1-7, subcutaneously); and G-CSF (5ug/kg/d, d1-7, subcutaneously) in 28-day cycles. The dose of venetoclax was adjusted based on concomitant moderate or strong CYP3A inhibitors. Efficacy was evaluated by bone marrow morphology and flow cytometry on day 28 of cycle 1. The primary and secondary end point were composite complete remission, MRD and safety, respectively.

Results: A total of 37 patients with AML were enrolled between January 1, 2023, and March 31, 2024, with a median age of 68 years (range, 53 to 87). Seventeen patients (46%) had adverse risk, 10 patients (27%) had intermediate risk, 9 patients (24%) had favorable risk, and 1 patient (3%) was not available. All patients completed at least 1 cycle of treatment (range: 1-8). Three patients were lost to follow-up after one cycle and two patients died during induction. The composite complete remission rate was 63% (20/32), and 14 patients (70%) were MRD negative by flow cytometry. The composite complete remission rates for the favorable-risk group, intermediate-risk group, and adverse-risk group were as follows: 89%(8/9), 33% (3/9) and 64%(9/14). Haematological adverse events of all grades occurred in most patients. The most common non-haematological adverse events of any grade included fatigue (51%, 19/37), constipation (43%, 16/37), febrile neutropenia (30%, 11/37), and pneumonia (20%, 7/37). All adverse events could be managed and improved through dose adjustments and supportive treatment.

Conclusion:The VAG regimen achieved high rates of complete remission and MRD negativity in unfit patients with newly diagnosed AML. This combined regimen has an acceptable safety profile, with low incidence of infection. A phase 2 study of VAG regimen has completed and a phase 3 trial comparing VAG vs VA regimen is undergoing currently by us.

Disclosures

No relevant conflicts of interest to declare.

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2024
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