An inhibitor drug that targets a specific mutation in relapsed or refractory acute myeloid leukemia (AML) helps patients live almost twice as long as those who receive chemotherapy. Researchers at Penn’s Abramson Cancer Center presented the findings of ADMIRAL—a randomized clinical trial investigating the drug gilteritinib in patients with a mutation in the Fms-like tyrosine kinase 3 (FLT3) gene—at the 2019 American Association for Cancer Research Annual Meeting. Alexander Perl, an associate professor of hematology-oncology in PSOM, led the trial. The drug was recently approved by the FDA as XOSPATA.

“Patients with FLT3 mutations who have relapsed or refractory AML have very low response rates to chemotherapy at the time of relapse, and their survival is poor as a result,” Dr. Perl said. “This drug is specifically designed to help this group of patients, and now we’ve shown it can make a huge difference for those who, until recently, had no specific therapies available beyond chemotherapy.”

FLT3 is the most commonly mutated gene in AML and is found in about 30% of patients’ leukemia cells. The FLT3 gene is expressed in normal bone marrow cells and regulates the orderly growth of blood cells in response to daily demands. When the gene is mutated in a leukemia cell, the cancer cells grow in an uncontrolled manner unless the function of FLT3 is turned off by drugs like gilteritinib.

In the ADMIRAL trial, 371 patients were randomized, with 247 receiving gilteritinib and 124 receiving chemotherapy. The patients who took gilteritinib had a median overall survival of 9.3 months compared to 5.6 months for the chemotherapy patients. At one year, 37% of patients on gilteritinib were still alive, compared to 16.7% of patients in the chemotherapy group. The combined rates of complete remissions (CR) or CR with partial hematologic recovery (CRh) were 34% for the gilteritinib arm and 15% for the chemotherapy arm.

“Although the incidence of various side effects was similar across the study arms, patients took gilteritinib for considerably longer than they underwent chemotherapy,” Dr. Perl said. “This actually means the likelihood of side effects on a daily basis is lower on this drug.”

Dr. Perl noted that the safety profile of the drug also means gilteritinib can be used not only to stabilize patients for a potentially curative bone marrow transplant, but also as an ongoing therapy following transplant in the hope of reducing the chance for relapse.