Adding gilteritinib to azacitidine did not improve survival outcomes in patients with newly diagnosed, FLT3-mutated acute myeloid leukemia (AML) who were ineligible for intensive induction chemotherapy, according to research published in Blood.

Researchers conducted a multicenter, open-label, randomized phase 3 trial to evaluate the efficacy and safety of gilteritinib plus azacitidine vs azacitidine in adults with newly diagnosed, FLT3-mutated AML ineligible for intensive induction chemotherapy ( Identifier: NCT02752035).

Patients were randomly assigned (2:1) to receive gilteritinib (120 mg/day orally) and azacitidine (75 mg/m2/day subcutaneously or intravenously on days 1-7) or azacitidine alone, on a 28-day cycle. The primary endpoint was overall survival (OS), and the key secondary efficacy endpoint was event-free survival (EFS).

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A total of 123 patients were included in the study, 74 in the gilteritinib-azacitidine arm (median age, 78 years; range, 59-90; 56.8% men) and 49 in the azacitidine arm (76 years; range, 61-88; 57.1% men). The percentage of patients with an ECOG performance status (PS) of 2 or higher was 47.3% in the gilteritinib-azacitidine arm and 32.7% in the azacitidine arm.

FLT3-ITD alone was detected in 78.4% of the gilteritinib-azacitidine arm and 81.6% of the azacitidine arm. FLT3-TKD alone was detected in 18.9% of the gilteritinib-azacitidine arm and 14.3% of the azacitidine arm. Both ITD and TKD mutations were detected in 2.7% of the gilteritinib-azacitidine arm and 4.1% of the azacitidine arm.

The researchers observed no significant difference in OS between the gilteritinib-azacitidine arm and the azacitidine arm. The median OS was 9.82 months and 8.87 months, respectively (hazard ratio [HR], 0.916; 95% CI, 0.529-1.585; P =.753). The study was closed based on the protocol-specified boundary for futility and recommendations from the independent data monitoring committee.

The researchers did note a numeric improvement in OS with gilteritinib-azacitidine in some patient subgroups, but statistical significance was not reached. Among patients with an ECOG PS of 0 to 1, the median OS was 13.17 months with gilteritinib-azacitidine and 11.89 months with azacitidine (HR, 0.811; 95% CI, 0.409-1.608; P =.549). Among patients with a FLT3-ITD allelic ratio of 0.5 or higher, the median OS was 10.68 months and 4.34 months, respectively (HR, 0.580; 95% CI, 0.285-1.182; P =.134).

The median EFS was 0.03 months in both treatment arms. However, the rate of composite complete remission was significantly higher in the gilteritinib-azacitidine arm than in the azacitidine arm (58.1% and 26.5%, respectively; P <.001).

Adverse event (AE) rates were similar between the arms. AEs of any grade occurred in 100% of patients in the gilteritinib-azacitidine arm and 95.7% of those in the azacitidine arm. The rate of grade 3 or higher AEs was 95.9% and 89.4%, respectively.

Disclosures: This research was supported by Astellas Pharma, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Wang ES, Montesinos P, Minden MD, et al. Phase 3 trial of gilteritinib plus azacitidine vs azacitidine for newly diagnosed FLT3mut+ AML ineligible for intensive chemotherapy. Blood. 2022;140(17):1845-1857. doi:10.1182/blood.2021014586

This article originally appeared on Hematology Advisor