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FLT3-ITD MRD dynamics predicted relapse risk and shaped response to gilteritinib maintenance in post-transplant AML. 

A study published in the May 2025 issue of Blood about MORPHO trial that evaluated gilteritinib vs placebo as maintenance therapy after hematopoietic cell transplantation (HCT) in individuals with FLT3-ITD–mutated acute myeloid leukemia (AML), focusing on pre- and post-transplant measurable residual disease (MRD).   

Researchers conducted a retrospective study to assess how pre- and/or post-HCT FLT3-ITD MRD affected survival outcomes.  

They used a highly sensitive FLT3-ITD assay to estimate the MRD in individuals undergoing HCT. A post hoc analysis was performed to assess the association between MRD levels, relapse-free survival (RFS), and relapse risk. Clonal kinetics were also examined to evaluate the behavior of FLT3-ITD clones before and after treatment.  

The results showed that gilteritinib maintenance therapy improved RFS among individuals who had detectable peri-HCT MRD, while no benefit was observed among individuals without detectable MRD. Higher MRD levels were associated with an increased risk of relapse and reduced RFS. In the placebo group, 42.2% of individuals with detectable FLT3-ITD MRD relapsed, compared to 13.4% without MRD. Multiple FLT3-ITD clones were identified in 14.8% of participants, who had poor survival across both treatment arms. Rapid relapse, often within weeks of post-HCT, was noted among individuals who were MRD-positive on placebo. For those receiving gilteritinib, relapse occurred with FLT3 wild-type clones, after gilteritinib discontinuation with persistent MRD, or due to progression of multiclonal disease.  

Investigators concluded that the detection of FLT3-ITD MRD, encompassing clonal burden and its changes over time, provided essential prognostic insights that could have guided post-HCT treatment approaches for patients with FLT3-ITD-mutated AML undergoing gilteritinib maintenance. 

Source: ashpublications.org/blood/article/145/19/2138/534969/Measurable-residual-disease-and