General Information

Xospata (gilteritinib) is a kinase inhibitor.

Xospata is specifically indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test.

Xospata is supplied as a tablet for oral administration. The recommended starting dose is 120 mg orally once daily with or without food. Response may be delayed. In the absence of disease progression or unacceptable toxicity, treatment for a minimum of 6 months is recommended to allow time for a clinical response. Do not break or crush Xospata tablets. Administer tablets orally about the same time each day. If a dose of Xospata is missed or not taken at the usual time, administer the dose as soon as possible on the same day, and at least 12 hours prior to the next scheduled dose. Return to the normal schedule the following day. Do not administer 2 doses within 12 hours.

Mechanism of Action

Xospata (gilteritinib) is a small molecule that inhibits multiple receptor tyrosine kinases, including FMS-like tyrosine kinase 3 (FLT3). Gilteritinib demonstrated the ability to inhibit FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3-ITD, tyrosine kinase domain mutations (TKD) FLT3-D835Y and FLT3-ITD-D835Y, and it induced apoptosis in leukemic cells expressing FLT3-ITD.

Side Effects

Adverse effects associated with the use of Xospata may include, but are not limited to, the following:

• myalgia/arthralgia
• transaminase increase
• fatigue/malaise
• fever
• noninfectious diarrhea
• dyspnea
• edema
• rash
• pneumonia
• nausea
• stomatitis
• cough
• headache
• hypotension
• dizziness
• vomiting

The Xospata drug label comes with the following Black Box Warning: Patients treated with Xospata have experienced symptoms of differentiation syndrome, which can be fatal if not treated. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

Clinical Trial Results

The FDA approval of Xospata was based on the ADMIRAL trial, which included 138 adult patients with relapsed or refractory AML having a FLT3 mutation. Xospata was given orally at a starting dose of 120 mg daily until unacceptable toxicity or lack of clinical benefit. Dose reductions were allowed, to manage adverse events, and dose increases were allowed, to increase clinical benefit. Efficacy was established on the basis of the rate of complete remission (CR)/complete remission with partial hematologic recovery (CRh), the duration of CR/CRh (DOR), and the rate of conversion from transfusion dependence to transfusion independence in the ADMIRAL trial. Among the 106 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 33 (31.1%) became independent of RBC and platelet transfusions during any 56-day post-baseline period. For the 32 patients who were independent of both RBC and platelet transfusions at baseline, 17 (53.1%) remained transfusion-independent during any 56-day post-baseline period. Twenty-one percent of patients achieved complete remission (no evidence of disease and full recovery of blood counts) or complete remission with partial hematologic recovery (no evidence of disease and partial recovery of blood counts) with treatment.