(225) The Analysis of Fms-like Tyrosine Kinase Inhibitor Maintenance Therapy Following Allogeneic Stem Cell Transplant in Patients with Fms-like Tyrosine Kinase-mutated Acute Myeloid Leukemia

Poster Abstract:

Background: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by clonal expansion of myeloid blasts in peripheral blood, bone marrow, and other tissues. Depending on prognosis and risk classification, AML patients may undergo allogeneic stem cell transplants (allo-SCT) following induction chemotherapy. Mutations of fms-like tyrosine kinase (FLT3) have been associated with an increased percentage of blast cells in peripheral blood and bone marrow leading to poorer prognosis. The FLT3 mutation is classified as unfavorable by the National Comprehensive Cancer Network (NCCN) guidelines with poor prognosis leading to lower remission rates and shorter periods of disease or event free states. FLT3 mutations are classified as tyrosine kinase domain point mutations (FLT3-TKD) or internal tandem duplications (FLT3-ITD). In allo-SCT, FLT3-ITD mutated patients have demonstrated poorer outcomes compared to FLT3 wild type. There is conflicting data of the prognostic effect FLT3-TKD mutations have in AML. Given the unfavorable impact FLT3 mutations have on AML prognosis after allo-SCT, FLT3 inhibitors have become key components of treatment in this population. There are currently four FLT3 inhibitors recommended as post-transplant maintenance therapy by the NCCN guidelines in AML patients with a history of a FLT3 mutation: midostaurin, sorafenib, quizartinib, and gilteritinib. There is currently no standardized recommendation on whether a specific FLT3 inhibitor should be used over another in the post allo-SCT maintenance setting. At Rush University Medical Center (RUMC), there is currently no standardized regimen or preferred FLT3 inhibitor in this setting with three of the agents being used in practice (midostaurin, gilteritinib, and sorafenib).

Objective: The main objective of this study is to assess the efficacy and safety of FLT3 inhibitors in the post-transplant setting with intention of creating a guideline for utilization at Rush University Medical Center (RUMC). This clinical guideline will assist providers in selecting a post allo-SCT maintenance agent with the appropriate monitoring.

Methods: This single center, retrospective, observational cohort study will include adult FLT3-mutated AML patients receiving FLT3-targeted maintenance therapy with midostaurin, gilteritinib, or sorafenib following allo-SCT at RUMC from January 2021 to September 2023. The primary outcome is the one-year progression free survival after FLT3-targeted therapy initiation. Secondary outcomes include overall survival, non-relapse mortality, relapse rate, relapse free survival, incidence of graft versus host disease, and incidence of adverse effects one year following initiation of FLT3-targeted maintenance therapy.

Results: Completed results will be presented during the poster presentation.
Discussion/

Conclusion: Conclusions will be presented during the poster presentation.

References (must also be included in final poster): 1. National Comprehensive Cancer Network. Acute Myeloid Leukemia (Version 5.2023).
2. Grafone T, Palmisano M, Nicci C, Storti S. An overview on the role of FLT3-tyrosine kinase receptor in acute myeloid leukemia: biology and treatment. Oncol Rev. 2012;6(1):e8
3. Kiyoi H, Kawashima N, Ishikawa Y. FLT3 mutations in acute myeloid leukemia: Therapeutic paradigm beyond inhibitor development. Cancer Sci. 2020;111(2):312-322.