Dr. Levis on Gilteritinib in Relapsed/Refractory FLT3-Mutated AML

Mark James Levis, MD, PhD, program leader of Hematologic Malignancies and Bone Marrow Transplant Program at Sidney Kimmel Comprehensive Cancer Center, and professor of oncology, Johns Hopkins Medicine, discusses an analysis of gilteritinib (Xospata) in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia (AML) harboring other common co-mutations or a high FLT3-internal tandem duplication (ITD) allelic ratio.

Following data from the phase III ADMIRAL study, which led to the FDA’s decision to approve gilteritinib in patients with relapsed/refractory FLT3-mutated AML, Levis and colleagues performed next-generation sequencing on 37 different mutated genes in AML to compare the effectiveness of gilteritinib with salvage chemotherapy.

From the data, four major cohorts emerged: NPM1 mutation, DNMT3A mutation, WT1 mutation and patients with both NPM1 and DNMT3A mutations. Overall, gilteritinib had a clearly greater response rate than chemotherapy across all cohorts, says Levis.

The results pertaining to allelic ratio were as expected, he adds. Those with a higher allelic ratio (≥ 0.77), and thus more tumor present, performed worse than those with a lower ratio. However, gilteritinib was found to confer longer OS compared with chemotherapy in patients with a high (7.1 months versus 4.3 months, respectively) or low FLT3-ITD allelic ratio (10.6 months versus 6.9 months, respectively).

The most intriguing piece of data, according to Levis, was a remarkably impressive OS of 10.8 months in gilteritinib-treated patients with both NPM1 and DNMT3A mutations compared with just 5 months in those who received chemotherapy. Levis says these data raise the question of whether gilteritinib should be moved into the upfront setting for these patients in the future.