Clinical Summary: 

• Design/Population: The phase 3 HOVON156/AMLSG28-18/PASHA trial randomized newly diagnosed patients with FLT3-mutated acute myeloid leukemia to receive intensive chemotherapy plus either gilteritinib or midostaurin, followed by consolidation, transplantation (when eligible), and FLT3 inhibitor maintenance.
• Key Outcomes: Gilteritinib did not significantly improve overall survival compared with midostaurin, despite reducing morphologic relapse risk and numerically prolonging event-free survival. Complete remission rates were similar, and safety was broadly comparable, although serious adverse events were somewhat more frequent with gilteritinib.
• Clinical Relevance: Midostaurin remains the standard frontline FLT3 inhibitor with intensive chemotherapy, though gilteritinib showed clinically meaningful relapse-free benefit.

Results from the phase 3 HOVON156/AMLSG28-18/PASHA trial demonstrate that gilteritinib did not significantly improve overall survival (OS) compared with midostaurin when combined with extensive chemotherapy among newly diagnosed patients with FLT3-mutated acute myeloid leukemia (AML). 

These results were presented by Marc Raaijmakers, MD, Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands, at the 2026 European Hematology Association (EHA) Congress in Stockholm, Sweden.

In this open-label study, 768 patients deemed fit for intensive chemotherapy were randomized 1:1 to receive induction and consolidation chemotherapy plus either 120 mg of once daily gilteritinib (n = 384) or 50 mg of twice daily midostaurin (n = 384), followed by FLT3 maintenance. The primary end point was OS. Key secondary end points included event-free survival (EFS), complete response after induction, relapse-free survival (RFS), and safety.

At a median follow-up of 43.2 months, median OS was not reached in either treatment arm (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.81 to 1.28; P = .864). Median EFS was 51.1 months in the gilteritinib arm and 19.9 months in the midostaurin arm (HR, 0.83; 95% CI, 0.68 to 1.02; P = .052).

Investigator-assessed complete response after induction was 79% in the gilteritinib arm and 83% in the midostaurin arm. Morphologic relapse after complete response occurred in 21% and 36% of patients, respectively (HR, 0.68; 95% CI, 0.54 to 0.88; P = .003). 

Among patients who relapsed, median OS was 7.2 months in the gilteritinib arm and 10.2 months in the midostaurin arm (HR, 1.54; 95% CI, 1.06 to 2.23; P = .022). Patients initially treated with midostaurin were substantially more likely to receive salvage gilteritinib (50% vs 17%) and undergo allogeneic transplantation (alloHSCT) after relapse (34% vs 22%). The 30-day mortality rate was 5% in the gilteritinib arm and 3% in the midostaurin arm, with 60-day mortality rates of 9% and 6%, respectively.  

Treatment-related adverse events were reported in 40% of patients in both treatment arms. Grade ≥3 treatment-related adverse events were reported in 23% of patients in the gilteritinib arm and 19% of patients in the midostaurin arm. Serious adverse events were reported in 68% and 59% of patients, respectively.

 “A clinically meaningful RFS advantage with [gilteritinib] vs [midostaurin] did not translate into an OS benefit, likely due to more frequent use of [gilteritinib] and alloHSCT as salvage therapy with [midostaurin],” concluded Dr Raaijmakers. 

Source: 

Raaijmakers M, Ossenkoppele G, Gradowska P, et al. Gilteritinib versus midostaurin in patients with newly diagnosed FLT3-mutated acute myeloid leukemia eligible for intensive therapy: Results from the phase 3 HOVON156/AMLSG28-18/PASHA trial. Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-7247.