Evaluating the clinical benefits and safety of FLT3 inhibitors in various treatment stages of acute myeloid leukemia.

This study investigated the clinical benefits and safety of FMS-like tyrosine kinase 3 inhibitors (FLT3i) in various treatment stages of acute myeloid leukemia (AML). The data showed that FLT3is safely improved prognosis in the induction stage (first-line treatment) of newly diagnosed FLT3-positive AML and salvage therapy (treatment given after first-line therapy had failed) of patients with relapsed or refractory (r/r) AML.

AML is a cancer of the blood and bone marrow leading to abnormal white blood cells. Certain genetic changes (mutations) 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 very poor prognosis. These patients are normally treated with allogeneic hematopoietic stem cell transplant (allo-HSCT) and salvage treatments. Allo-HSCT involves taking stem cells from one person and transplanting them into the AML patient to allow the development of new blood cells. However, many patients experience relapse (worsening of the disease) or refractory (not responsive to the treatment) after allo-HSCT. Patients with r/r AML usually benefit from salvage therapies.

Patients can also receive maintenance treatment to prevent relapse. FLT3i is a type of targeted therapy known as tyrosine kinase inhibitors (TKIs). TKIs such as sorafenib (Nexavar) and midostaurin (Rydapt) have been shown to be effective in patients with relapsed FLT3-mutated AML. However, there are very few studies investigating the clinical benefits and safety of FLT3i in various treatment stages of AML.

This study analyzed 39 studies and involved 6859 patients with FLT3-positive AML. Patients were divided into FLT3i group and non-FLT3i group according to the therapy they receievd.

Patients in the FLT3i group with newly diagnosed AML were 12% more likely to have complete remission than those in the non-FLT3i group. Patients in the FLT3i group with r/r AML were 39% more likely to have complete remission than those in the non-FLT3i group.

Patients in the FLT3i group with newly diagnosed AML were 24% more likely to have a better survival and 28% more likely to survive without cancer worsening than those in the non-FLT3i group. Patients in the FLT3i group with r/r AML were 40% more likely to have a better survival and 60% more likely to survive without cancer worsening than those in the non-FLT3i group.

Patients with FLT3(+) AML who received allo-HSCT treatment were 47% more likely to have a better survival and 43% more likely to survive without cancer worsening than those who did not receive allo-HSCT treatment.  These patients when given FLT3i were then 55% more likely to have a better survival and 66% more likely to survive without cancer worsening than those who did not receive FLT3i.

The most common side effects associated with FLT3i were low blood cell countss, skin and heart-related effects.

This study concluded that FLT3is safely improved prognosis in the induction/salvage stage of patients with FLT3-positive AML and increased survival benefits after allo-HSCT as maintenance therapy.

Most of the studies analyzed looked back in time at medical records. This study did not make a subgroup analysis based on which FLT3i has the best outcomes. Further studies are needed to explore the full benefits of FLT3i in AML.