Gilteritinib Maintenance Shows Benefit in MRD-Positive AML

By Cecilia Brown - Last Updated: July 19, 2023

Gilteritinib “appears to have a clear benefit” for patients with FLT3-ITD acute myeloid leukemia (AML) who have measurable residual disease (MRD) before or after hematopoietic stem cell transplantation (HSCT), according to results from a phase III study.

Mark Levis, MD, PhD, of Johns Hopkins University, and colleagues conducted the study and presented their findings during the 2023 European Hematology Association Congress.

They conducted the research because patients with AML who have FLT3-ITD have a “high risk of relapse” and “routinely undergo” allogeneic HSCT.

FLT3 inhibitors are often administered as post-[HSCT] maintenance therapy to decrease relapse risk, but this practice is based on randomized studies of sorafenib that included patients salvaged with FLT3 inhibitors pretransplant,” Dr. Levis and colleagues wrote.

The BMT-CTN1506 trial, also known as the MORPHO trial, was a randomized, placebo-controlled study that evaluated the use of gilteritinib as post-transplant maintenance. The primary objective of the study was to determine if gilteritinib maintenance improved relapse-free survival (RFS) over placebo for patients with FLT3-ITD AML who received allogeneic HSCT in their first remission. Secondary objectives included overall survival (OS), examining the effect of MRD status before and after transplant on RFS and OS, nonrelapse mortality rates, event-free survival, and graft-versus-host disease (GVHD).

The study included 356 patients with FLT3-ITD AML who were in their first remission after no more than two cycles of induction therapy and had HSCT planned within 12 months. After patients received induction and consolidation therapy, they were registered and underwent HSCT. Following engraftment, which took place 30 to 90 days after HSCT, the researchers randomized patients to receive placebo or gilteritinib 120 mg daily for 24 months. They collected marrow aspirates for MRD before transplant, before randomization, and at three, six, 12, 18, and 24 months after randomization.

The RFS was higher for patients who received gilteritinib than in those who received placebo in an intention-to-treat analysis, but the difference was not significant (hazard ratio [HR], 0.679; 95% CI, 0.459, 1.005; two-sided P=.0518). The OS was similar between groups (HR, 0.846; 95% CI: 0.554, 1.293; two-sided P=.4394). The two-year RFS rate was 77.2% in patients receiving gilteritinib, while it was 69.9% in those receiving placebo.

Half (50.6%) of the patients had detectable MRD before transplant or before randomization. Dr. Levis and colleagues reported the “effect of gilteritinib was more pronounced” in patients who had detectable MRD (HR, 0.515, 95% CI, 0.316, 0.838; P=.0065) than in those without detectable MRD (HR, 1.213, 95% CI, 0.616, 2.387, P=.575).

Dose interruptions occurred in 80.3% of patients receiving gilteritinib and in 72.9% of patients receiving placebo. Around half (54.5%) of the patients receiving gilteritinib required dose reductions, while 25.4% of patients receiving placebo required dose reductions.

Treatment-emergent adverse events (AEs) were more common in patients receiving gilteritinib, as well as treatment-emergent AEs that led to withdrawal of treatment. Neutrophil decrease occurred in 42.1% of patients receiving gilteritinib, nearly triple the rate of 15.8% in patients receiving placebo. Chronic GVHD occurred in 52.2% of patients receiving gilteritinib and in 42.1% of patients receiving placebo.

“Gilteritinib appears to have a clear benefit for the 50% of [patients] with detectable MRD pre- or post-[HSCT], compared to those without detectable MRD. [Treatment-emergent] AEs associated with gilteritinib were primarily myelosuppression and increased incidence of chronic GVHD,” Dr. Levis and colleagues concluded. “These data are among the first to support the effectiveness of MRD-based post-[HSCT] maintenance therapy.”


Levis MJ, Hamadani M, Logan B, et al. BMT-CTN 1506 (MORPHO): a randomized trial of the FLT3 inhibitor gilteritinib as post-transplant maintenance for FLT3-ITD AML. Abstract #LB2711. Presented at the 2023 European Hematology Association Congress. June 8-15, 2023; Frankfurt, Germany.

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