FLT3 inhibitors as maintenance therapy post allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients with FLT3 mutations: A meta‐analysis

BACKGROUND: Acute myeloid leukemia (AML) patients with a Fms‐like tyrosine kinase 3 (FLT3) mutation have a high incidence of relapse despite allogeneic hematopoietic stem cell transplantation (allo‐HSCT) and a subsequent poor prognosis. FLT3 inhibitors (FLT3i) have been suggested to reduce the post‐transplant relapse risk in recent studies. As more evidence is accumulated, we perform the present meta‐analysis to assess the efficacy and safety of FLT3i as post‐transplant maintenance therapy in AML patients. METHODS: Literature search was performed in public databases from inception to December 31, 2021. Overall survival (OS), relapse‐free survival (RFS), cumulative incidence of relapse (CIR), non‐relapse mortality (NRM), graft‐versus‐host disease (GVHD) and adverse events were compared between FLT3i and control groups. Pooled hazard ratio (HR) or relative risk (RR) with corresponding 95% confidence interval (CI) were calculated. RESULTS: We identified 12 eligible studies with 2282 FLT3‐mutated AML patients who had received HSCT. There was no between‐study heterogeneity and a fix‐effect model was used. Post‐transplant FLT3i maintenance significantly prolonged OS (HR = 0.41, 95%CI: 0.32–0.52, p < 0.001) and RFS (HR = 0.39, 95%CI 0.31–0.50, p < 0.001), and reduced CIR (HR = 0.31, 95%CI 0.20–0.46, p < 0.001) as compared with control. There were no significant risk differences in NRM (RR = 0.69, 95%CI 0.41–1.17, p = 0.169), acute GVHD (RR = 1.17, 95%CI 0.93–1.47, p = 0.175), chronic GVHD (RR = 1.31, 95%CI 0.91–1.39, p = 0.276) and grade ≥3 adverse events between both groups, except for skin toxicity (RR = 5.86, 95%CI 1.34–25.57, p = 0.019). CONCLUSION: Post‐transplant FLT3i maintenance can improve survival and reduce relapse in FLT3‐mutated AML patients and is tolerable.