ATLANTA (GenomeWeb) – Treatment with a FLT3 inhibitor improved survival among patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 mutation, according to data presented at the American Association for Cancer Research annual meeting here.
"This is a new practice-changing strategy that is something that we have been needing in the field of acute myelogenous leukemia therapy," Louis Weiner, the director of the Georgetown Lombardi Comprehensive Cancer Center, who was not part of the study, said during a press briefing.
There are some 19,520 cases of AML in the US each year, according to the National Cancer Institute. About 40 percent of AML patients don't respond to primary treatment and another 40 percent to 70 percent relapse after initial treatment with chemotherapy and remission.
Nearly a third of AML patients harbor mutations in FLT3, typically an internal tandem duplication (ITD), which is associated with early relapse risk, rapid tumor doubling times, and poor survival.
"This is a highly aggressive disease that we unfortunately don't have very good therapeutics to treat in terms of standard, approved therapies," said Alexander Perl, an associate professor of hematology/oncology at the University of Pennsylvania, during a press briefing announcing the results from the phase 3 ADMIRAL trial. The trial was funded by Astellas Pharma.
Late last year, based on safety and interim results from the ADMIRAL trial, the US Food and Drug Administration approved the type 1 FLT3 inhibitor gilteritinib (Xospata) from Astellas Pharma for patients with relapsed or refractory AML with FLT3 mutations. At the same time, the agency expanded the indication for the LeukoStrat CDx FLT3 Mutation Assay from Invivoscribe Technologies as a companion diagnostic.
Perl has now announced survival data from the trial, which he noted shows patients who took gilteritinib exhibited better survival times than those who received standard chemotherapy regimens. Gilteritinib, he added, is a potent inhibitor of both FLT3-ITD and FLT3-tyrosine kinase domain (TKD) mutations that can arise following quizartinib and sorafenib treatment.
The ADMIRAL trial was a randomized, phase 3 clinical trial that aimed to gauge whether gilteritinib improved survival for patients with relapsed or refractory FLT3-mutated AML. Patients with such disease were randomized to either receive daily oral gilteritinib or salvage chemotherapy, with investigators choosing the appropriate type of chemotherapy prior to randomization.
There were 247 patients in the gilteritinib arm and 124 in the chemotherapy arm, and patients in both arms could also receive hematopoietic stem cell transplants.
Of these patients, 146 had primary refractory disease and 225 had relapsed.
Additionally, 88 percent of patients had FLT3-ITD mutations alone, 8 percent had FLT3-TKD mutations alone, and 2 percent had both types of FLT3 mutations.
Overall, patients in the trial who received gilteritinib had a 36 percent reduction in their risk of death, as compared to patients who received salvage chemotherapy. In particular, gilteritinib-treated patients had a median overall survival of 9.3 months, while patients who received salvage chemotherapy had a median overall survival of 5.6 months. Further, the overall survival rate at 12 months was 37 percent of the gilteritinib arm, as compared to 17 percent for the salvage chemotherapy arm.
According to Perl, the treatment was also well tolerated among patients and was linked to lower toxicity in the first 30 days of treatment, as compared to chemotherapy.
"Gilteritinib, a targeted inhibitor of FLT3, improves both response and survival of patients with FLT3-mutated relapse and refractory AML," Perl said. "This is a major change in how we approach patients in the relapse and refractory setting because now we are using molecularly targeted therapy to select patients who can benefit from this approach."
Perl argued that this drug could establish a new standard of care for this patient cohort. He added that studies adding gilteritinib to front-line treatment are underway.