Evaluating combined treatment of venetoclax and gilteritinib for relapsed or refractory acute myeloid leukemia with the FLT3 mutation.

This study evaluated the tolerability and effectiveness of combined therapy using venetoclax (Venclexta) and gilteritinib (Xospata) in patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) with the FLT3 (FMS-related tyrosine kinase 3) mutation. The data showed that a combination of venetoclax and gilteritinib potentially improved treatment responses over standard therapy in these patients.

AML is a cancer of the blood and bone marrow associated with the rapid growth of abnormal cells that interfere with normal blood cell production.  Venetoclax is a BCL-2 inhibitor that promotes the death of leukemia cells. It is approved as standard therapy for use with low-dose cytarabine (Cytosar-U) or hypomethylating agents in newly-diagnosed patients with AML.

The FLT3 gene mutation commonly occurs in AML. The FLT3 gene codes for the FLT3 protein that causes immature blood cells to grow rapidly. AML treatments such as venetoclax have shown limited effectiveness in these patients. These patients usually develop r/r disease.

Gilteritinib is an orally-administered FLT3 inhibitor approved for use in patients with r/r AML with FLT3 activating mutations (FLT3^mut). It has been shown to improve patient responses and survival rates. However, many patients are unable to have deep and durable responses. There is a need to investigate whether venetoclax combined with gilteritinib (VenGilt) would provide better patient outcomes compared to standard treatment in these patients.

This study included 61 patients with r/r AML. 56 patients had AML with FLT3^mut. Prior FLT3 inhibitor therapy was received by 36 patients of these 56 patients. 19 patients had prior stem cell transplant (SCT) therapy. 10 patients had prior venetoclax therapy. No patients had prior gilteritinib therapy. Patients were given 400 mg of once-daily, orally-administered venetoclax and 80 mg or 120 mg of once-daily, oral gilteritinib. Patients were evaluated for safety and treatment responses for 17.5 months.

Complete responses occurred in 75% of patients with the FLT3^mut. Similar responses occurred for patients with or without prior FLT3 inhibitor therapy. The average time to respond was 0.9 months. The average length of remission was 4.9 months.

97% of patients experience severe side effects. The most commonly observed side effects due to treatment were low blood cell counts.

This study concluded that high-risk patients with AML and the FLT3 mutation possibly benefited from combination therapy with orally-administered venetoclax and gilteritinib compared to standard treatment alone.

The study involved a small number of patients. There was no comparison group. This study was funded by AbbVie, the manufacturer of venetoclax.