Impact of FMS-like tyrosine kinase 3 inhibitor maintenance on post-transplant outcomes in acute myeloid leukemia with FMS-like tyrosine kinase 3 mutations: a real-world German registry analysis highlighting sorafenib

Abstract

FLT3-mutation occurs in 25-30% of AML and confers high relapse risk and inferior survival. Allogeneic hematopoietic cell transplantation (allo-HCT) offers curative potential, yet relapse remains a major post-transplant challenge. Maintenance therapy with FLT3 inhibitors (FLT3i) after allo-HCT has emerged as a promising strategy, but real-world evidence remains limited. This study aimed to assess the impact of FLT3i maintenance on transplant outcomes. We analyzed 523 adults with FLT3-ITD AML in first complete remission who underwent allo-HCT between 2011 and 2023 in 13 German transplant centers participating in the national DRST registry; 22% received FLT3i maintenance (sorafenib 49%, midostaurin 37%, gilteritinib 5%, unknown 9%). In multivariable analyses (MVA), FLT3i maintenance improved OS (HR 2.25, 95% CI [1.28; 3.95], p=0.005), RFS (HR 1.72, 95% CI [1.05; 2.81], p=0.030), non-relapse mortality (HR 3.62, 95% CI [1.08; 12.11], p=0.037), and GVHD- and relapse-free survival (HR 1.59, 95% CI [1.06; 2.40], p=0.025). The cumulative incidence of relapse did not differ. In univariate analyses (UVA), OS benefits were observed in MRD-positive (HR 2.35, 95% CI [1.04; 5.31], p=0.025) and MRD-negative patients (HR 2.64, 95% CI [1.05; 6.68], p=0.020. Sorafenib maintenance (n=50) demonstrated superior efficacy with 5-year OS of 85% versus 62% (HR 2.979, p=0.0045) and RFS of 84% versus 55% (HR 2.771, p=0.0043) compared to no maintenance. These real-world findings, while limited by the retrospective design and potential selection bias, align with randomized trial data and support the use of FLT3i maintenance as part of post-transplant care for FLT3-ITD AML.