Study Found Gilteritinib Superior to Salvage Chemotherapy in FLT3-mutated Refractory AML

Gilteritinib may more effectively improve survival in patients with FLT3-mutated relapsed or refractory acute myeloid leukemia (R/R AML) who have common comutations or a high FLT3-ITD allelic ratio compared with salvage chemotherapy, according to data presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In a phase 3, open-label, multicenter randomized trial (ClinicalTrials.gov Identifier: NCT02421939), 371 participants with FLT3-mutated relapsed or refractory AML were randomized 2:1 to receive continuous 28-day cycles of 120mg/day gilteritinib or salvage chemotherapy.

For the part of the study presented at the 2019 ASCO Meeting, the researchers examined 37 recurrently mutated genes in AML using next-generation sequencing. The authors used the value of greater than or equal to 0.027 as the cutoff for comutation positivity. 

The investigators measured baseline FLT3-ITD allelic ratio by the LeukoStrat CDx FLT3 Mutation Assay. The researchers used the median value of 0.77 to define FLT3-ITD allelic ratio as high when it was greater than or equal to 0.77, and low when it was less than 0.77.

After examining 361 patients, the researchers identified 4 major groups with specific comutations; 173 patients (47.9%) had NPM1, 115 patients (31.9%) had DNMT3A, 86 patients (23.8%) had DNMT3A/NPM1, and 65 patients (18%) had WT1. Moreover, 7 people (1.9%) had 3 simultaneous comutations, such as NPM1, DNMT3A, and WT1.

Patients who received gilteritinib had superior response rates and overall survival across all the 4 major comutation groups; the greatest survival benefit was found in patients with DNMT3A/NPM1 comutation (overall survival was 10.8 months in the gilteritinib arm versus 5 months in the salvage chemotherapy arm).

In patients with a high or low FLT3-ITD allelic ratio, gilteritinib resulted in longer overall survival than salvage chemotherapy. Among patients with a high FLT3-ITD allelic ratio, overall survival was 7.1 months in the gilteritinib arm compared with 4.3 months in the salvage chemotherapy arm. 

“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, Maryland.

Among those with a low FLT3-ITD allelic ratio, overall survival was 10.6 months in the gilteritinib arm compared with 6.9 months in the salvage chemotherapy arm.

Overall survival was longer in participants with a low FLT3-ITD allelic ratio than those with a high ratio across both arms; however, the difference in the gilteritinib arm was not significant (gilteritinib: hazard ratio [HR], 1.341; P =.0712; salvage chemotherapy: HR, 2.01; P =.0021).

References 

1. Levis MJ, Perl AE, Martinelli G, et al. Effect of gilteritinib on survival in patients with FLT3-mutated (FLT3^mut+) relapsed/refractory (R/R) AML who have common AML co-mutations or a high FLT3-ITD allelic ratio. Presented at 2019 ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 7000.
2. Perl AE, Martinelli G, Cortes JE, et al. CT184 – gilteritinib significantly prolongs overall survival in patients with FLT3-mutated (FLT3^mut+) relapsed/refractory (R/R) acute myeloid leukemia (AML): results from the phase III ADMIRAL trial. Presented at the American Association for Cancer Research Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. Abstract CTPL04.

This article originally appeared on Cancer Therapy Advisor