Sorafenib Maintenance Post-AlloHSCT Significantly Improves Survival, Reduces Relapse Rate Among Patients With FLT3-ITD-Mutated AML

Updated Results from a Randomized Phase 3 Trial 

In an updated post-hoc analysis from a phase 3 trial, sorafenib maintenance after allogeneic hematopoietic stem-cell transplantation (alloHSCT) significantly improved long-term survival and reduced relapse rate among patients with FLT3 internal tandem duplication (ITD)-mutated acute myeloid leukemia (AML) undergoing transplantation. 

The open-label, multicenter phase 3 trial enrolled a total of 202 patients with FLT3-ITD mutated AML undergoing alloHSCT with composite complete remission before and after transplantation plus hematopoietic recovery within 60 days after transplantation. Patients were randomly assigned to either the sorafenib maintenance group (n = 100) or a non-maintenance control group (n = 102). The primary end point was the cumulative incidence of relapse at 1 year. A post-hoc analysis took place after 5 years of follow-up.

These extended follow-up analyses showed improved overall survival, leukemia-free survival, and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) among patients who received sorafenib maintenance compared to the control group. Similarly, patients who received sorafenib maintenance exhibited a lower cumulative incidence of relapse (15%) versus the control (36.3%) and a comparable non-relapse mortality (15% versus 14.7%). There was no distinct difference between the 5-year cumulative incidence of chronic GVHD across groups, and there were no significant differences in late effects. No treatment-related deaths were reported. 

“With extended follow-up, sorafenib maintenance after transplantation is associated with improved long-term survival and reduced relapse rates compared with non-maintenance, further supporting this strategy as a standard of care for patients with FLT3-ITD acute myeloid [leukemia] undergoing allogeneic HSCT,” the study authors concluded. 

Source: 

Xuan L, Wang Y, Yang K, et al. Sorafenib maintenance after allogeneic haemopoietic stem-cell transplantation in patients with FLT3-ITD acute myeloid leukaemia: long-term follow-up of an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol. Published online July 3, 2023. doi:10.1016/S2352-3026(23)00117-5