Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Acute Myeloid Leukemia.
Treatment: Xospata 40 MG OR TABS
The insurer denied Xospata 40 mg OR TABS.
The determination is overturned.

The patient was diagnosed with acute myeloid leukemia (AML) and has now completed 4 of 5 cycles of chemotherapy per Children's Oncology Group (COG) protocol. He remains in remission but is currently pancytopenic with early evidence of myeloid recovery but remains platelet transfusion dependent.
The patient has documented FLT-3 internal tandem duplication (ITD) internal tandem duplication. He has received treatment with asparaginase, cytarabine, daunorubicin, etoposide, gemtuzumab and mitoxantrone. He is currently in remission but remains a high-risk patient for relapse or recurrence due to his FLT-3/ITD status. This FLT-3 positive genetic alteration is known to be very high risk with a poor prognosis.
The primary oncologist considered adding midostaurin to his chemotherapy regimen. Midostaurin is Food and Drug Administration (FDA) approved for FLT-3 mutated patients, but its major side effect is cardiac arrythmias and prolonged QTc intervals. The patient experienced prolonged QTc when he was treated with midostaurin which is a contraindication to continued use. The drug was stopped in this patient due to this toxicity.
The treating oncologist is requesting use of Xospata (gilteritinib) instead of midostaurin in this patient with FLT3 mutated pediatric AML. There is now a Phase 3 Children's Oncology Group National Cancer Institute (NCI) approved protocol using this drug in FLT3 positive AML in pediatrics. At issue is whether the Xospata is likely to be more beneficial than any standard treatment or treatments for the insured's life threatening or disabling condition or disease.
The use of this drug, Xospata is likely to be more beneficial to this patient than any standard treatment for this patient's life threatening disease of FLT3+ AML. The use of this drug in this patient is indicated so that he can take this medication in order to improve his chances of overall survival. The clinical trial data in both adults and pediatrics supports the use of this drug in these patients as it has been shown to improve the overall survival of these high risk patients.
The pediatric data and clinical trial results for gilteritinib in FLT3+ AML supports the use of this drug in this patient. He also falls into the age range for the AYA (Adolescent Young Adult) cohort. Use of pediatric and/or adult clinical trials is supported in the AYA population. This patient is an AYA by definition as well.
Mutations in the FLT-3 gene result in constitutive activation of the FLT3 receptor tyrosine kinase which leads to uncontrolled cellular proliferation. The use of targeted tyrosine kinase inhibitors has been shown to be a treatment strategy in both adults and children. In a current open Phase III Children's Oncology Group National Cancer Institute (NCI) approved clinical trial for newly diagnosed AML in children (AAML1831), those children who have FLT3 mutations will be eligible to receive gilteritinib as part of their treatment regimen. The expectation is the gilteritinib' s optimized properties including pharmacokinetic, potency and selectivity and favorable safety profile will result in improved outcomes in childhood AML containing FLT3/ITD+ alterations.
Children with FLT3+ AML who took midostaurin had a 22% lower death rate than those on the control arm. Both sorafenib and midostaurin have significant incident of systemic toxicities limiting their use. The next-generation FLT3 inhibitors, like gilteritinib, have been shown in early clinical trials to be safer and have excellent responses. Single agent gilteritnib demonstrated anti-leukemia activity in FLT3 mutant AML with an overall response rate of 55%.
The dose of gilteritinib has been determined in the safety phase of this study to be 2 milligrams/kilogram (mg/kg)/dose daily with a 120 mg maximum daily dose.
This phase III trial compares standard chemotherapy to therapy with CPX-351 [mixture of 2 chemotherapy] drugs (daunorubicin and cytarabine) and/or gilteritinib for patients with newly diagnosed acute myeloid leukemia with or without FLT3 mutations. Drugs used in chemotherapy, such as daunorubicin, cytarabine, and gemtuzumab ozogamicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. CPX-351 is made up of daunorubicin and cytarabine and is made in a way that makes the drugs stay in the bone marrow longer and could be less likely to cause heart problems than traditional anthracycline drugs, a common class of chemotherapy drug. Some acute myeloid leukemia patients have an abnormality in the structure of a gene called FLT3. Genes are pieces of deoxyribonucleic acid (DNA) (molecules that carry instructions for development, functioning, growth and reproduction) inside each cell that tell the cell what to do and when to grow and divide. FLT3 plays an important role in the normal making of blood cells. This gene can have permanent changes that cause it to function abnormally by making cancer cells grow. Gilteritinib may block the abnormal function of the FLT3 gene that makes cancer cells grow. The overall goals of this study are, 1) to compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people with newly diagnosed AML to find out which is better, 2) to study the effects, good and/or bad, of adding gilteritinib to AML therapy for patients with high amounts of FLT3/ITD or other FLT3 mutations and 3) to study changes in heart function during and after treatment for AML. Giving CPX-351 and/or gilteritinib with standard chemotherapy may work better in treating patients with acute myeloid leukemia compared to standard chemotherapy alone.