Measurable residual disease status and FLT3 inhibitor therapy in patients with FLT3-ITD mutated AML following allogeneic hematopoietic cell transplantation

Measurable residual disease (MRD) is associated with poor prognosis in acute myeloid leukemia (AML), even after allogeneic hematopoietic cell transplantation (HCT). New next-generation sequencing (NGS) methods have emerged as a highly sensitive and specific method to detect MRD. In addition to defining the role of post-HCT MRD monitoring in FLT3-ITD mutated AML, there is great interest in the optimal use of oral FLT3 tyrosine kinase inhibitors (FLT3 inhibitors) to maintain remission following HCT. In this study, we evaluated the clinical impact of sensitive FLT3 MRD testing early after HCT and maintenance FLT3 inhibitor use at our transplant center. We found that there was a trend towards inferior progression-free survival (PFS) for patients with early post-HCT MRD, but that overall survival (OS) was not significantly impacted by MRD. The use of maintenance FLT3 inhibitors led to a significantly superior PFS and OS in our cohort, and improved PFS and OS in both MRD-negative and MRD-positive patients. Altogether, our results demonstrate the prognostic significance of NGS-based MRD monitoring for FLT3-ITD and the ability of post-HCT maintenance therapy to prevent relapse and death in FLT3-ITD mutated AML.

Automated summary

Measurable residual disease is associated with poor prognosis in AML, and new NGS methods are highly sensitive in detecting MRD. The use of FLT3 inhibitors post-HCT is crucial for maintaining remission. Early post-HCT MRD negatively impacts PFS, while maintenance FLT3 inhibitors lead to superior PFS and OS for both MRD-negative and MRD-positive patients.