Gilteritinib Proves More Effective Than Salvage Chemotherapy in FLT3-Mutated Refractory AML

Researchers presented at ASCO’s 2019 Annual Meeting on the clinical benefits of gilteritinib FLT3-Mutated relapsed or refractory acute myeloid leukemia (R/R AML) compared with salvage chemotherapy. 

The phase 3, open-label, multicenter randomized trial examined 37 recurrently mutated genes in 361 patients using next generation sequencing, with a comutation positivity cutoff ≥0.027. Baseline FLT3-ITD AR was measured by the LeukoStrat CDs FLT3 Mutation Assay using a median value of 0.77 as the benchmark for a high vs low allelic ratio. 

Participants of the trial were randomized 2:1 to receive continuous 28-day cycles of 120mg/day gilteritinib or salvage chemotherapy.

Specific comutations divided trial participants into 4 distinct groups: 47% had  NPM1, 31.9% had DNMT3A, 23.8% had DNMT3A/NPM1, and 18% had WT1. Only 1.9% had all three NPM1, DNMT3A, and WT1 comutations. 

Across all 4 comutation groups, patients who received gilteritinib experienced superior response rates and improved survival. Those who received gilteritinib with the DNMT3A/NPM1 comutation had the greatest overall survival  rate of 10.8 months vs 5 months with salvage chemotherapy. 

Both high and low FLT3-ITD allelic ratio groups saw improved overall survival with gilteritinib compared with salvage chemotherapy, 7.1 months vs 4.3 months respectively. Patients with low FLT3-ITD exhibited OS of 10.6 months vs 6.9 months. OS was longer in the low FLT3-ITD AR cohort than the high FLT3-ITD AR cohort but the difference in the gilteritinib arm was not statistically significant (gilteritinib: HR=1.341, P=0.0712; SC: HR=2.01, P=0.0021), according the abstract.

“When you look at the overall survival for high allelic ratio, gilteritinib is clearly much better than chemo,” said lead study author Mark James Levis, MD, PhD, a professor of oncology at Johns Hopkins Medicine in Baltimore, MD.—Edan Stanley