Evaluating the effectiveness and safety of gilteritinib plus azacitidine versus azacitidine alone for patients with newly diagnosed FLT3-mutated acute myeloid leukemia.

This study investigated the effectiveness and safety of gilteritinib (Xospata) plus azacitidine (Vidaza) versus azacitidine alone for patients with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) who are unfit for intensive chemotherapy. The data showed that gilteritinib plus azacitidine significantly increased the complete remission rates with similar overall survival compared to azacitidine alone and was safe with manageable side effects in these patients.

AML is a cancer of the blood and bone marrow leading to abnormal white blood cells. Some patients respond to treatments, such as chemotherapy but the cancer returns. This is called relapsed AML. Some patients do not respond to treatments, and this is called refractory AML. Azacitidine is a chemotherapy drug used for the treatment of AML.

Certain genetic changes in AML can make it more difficult to treat. About 30% of adults with newly diagnosed AML show a duplication (a type of mutation) on the FMS-like tyrosine kinase 3 (FLT3) gene. Patients with the FLT3 mutation often have a poorer prognosis. FLT3i is a type of targeted therapy known as tyrosine kinase inhibitors (TKIs). TKIs such as gilteritinib have been shown to be effective in patients with relapsed or refractory FLT3-mutated AML. However, the effectiveness and safety of gilteritinib plus azacitidine versus azacitidine alone for patients with newly diagnosed FLT3-mutated AML who are unfit for intensive chemotherapy are still unknown.

This study involved 123 patients with FLT3-positive AML who were unfit for intensive chemotherapy. Patients were randomly assigned into two groups. Group 1 included 74 patients who received gilteritinib plus azacitidine. Group 2 included 49 patients who received azacitidine alone. Patients were followed up for an average of 9.76 months. 

The average overall survival was 9.82 months in group 1 versus 8.87 months in group 2. This difference was not statistically significant.

58.1% of the patients in group 1 achieved complete remission compared to 26.5% of the patients in group 2. This difference was statistically significant.

The rate of serious side effects was 95.9% in group 1 versus 89.4% in group 2. The most common side effects were fever (47.9%) and diarrhea (38.4%).

This study concluded that gilteritinib plus azacitidine significantly increased the complete remission rates with similar overall survival compared to azacitidine alone and was safe with manageable side effects for patients with FLT3-mutated AML.

This study was funded by Astellas Pharma Inc., the manufacturer of gilteritinib.