Outcomes of post-allogeneic hematopoietic stem cell transplant (HSCT) maintenance therapy in FLT3-mutated, IDH-mutated, or high relapse-risk myeloid malignancies: A single-center experience.

e18559 Background: Allogeneic hematopoietic stem cell transplant (HSCT) is potentially curative in acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS), though post-HSCT relapse remains the leading cause of treatment failure. There is a lack of consensus on the role of maintenance FLT3/IDH inhibitors and decitabine post-HSCT. Methods: We retrospectively reviewed patients at our institution who underwent allogeneic HSCT for AML and HR-MDS, with FLT3 mutations, IDH mutations or high-relapse risk features (primary refractory AML, measurable residual disease pre- or post-transplant, high-risk mutations or cytogenetics, and transplant at ≥ 2nd complete remission). We describe use of FLT3/IDH inhibitors and decitabine as post-HSCT maintenance. We report infection rates within 3 months of therapy and relapse-free survival (RFS) and overall survival (OS) using logrank test. Results: From November 2021 to July 2024, 32 patients received maintenance post-transplant. The median age at diagnosis was 67 years and 66% were males. Eight patients with FLT3-ITD/TKD mutations received gilteritinib starting at 40 mg with 22% reaching the goal dose of 120 mg. One patient stopped therapy due to acute kidney injury and QTc prolongation and 3 patients remained at 80 mg due to cytopenia, neuropathy, and dizziness. Quizartinib was started on 1 patient at 17.7 mg with a plan to increase to 53 mg. Median treatment duration was 338 days with 100% RFS and OS at 24 months, and 2 infections (norovirus enteritis, atypical pneumonia). Ivosidenib was started at 500 mg in 2 patients with IDH1 mutations. There was 1 dose reduction due to dizziness. Enasidenib was started at 100 mg in 8 patients with IDH2 mutations with none needing dose reductions. Overall, median treatment duration was 492 days, with 91% RFS and 100% OS at 24 months, and 2 infections (urinary tract infection, influenza pneumonia). Fourteen patients with high-risk disease received decitabine at 10mg/m2 for 5 days (n= 12) or oral decitabine/cedazuridine 35/100mg/day for 2 days (n= 2) every 6 weeks, aiming for 6-9 cycles. Median number of cycles was 7 and 21% had a delay or dose reduction due to neutropenia/infection (influenza pneumonia, UTI). At 39 months, RFS was 61% and OS was 76.2%. Conclusions: Post-HSCT maintenance therapy, with small molecule inhibitors in AML with FLT3/IDH mutations and with decitabine in high-relapse risk AML/HR-MDS, appears well tolerated with excellent survival indices, especially in FLT3 and IDH mutated cohorts. This warrants further investigation into optimizing post-HSCT maintenance strategies.