Andreas Burchert, MD University Hospital Giessen and Marburg Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3–Internal Tandem Duplication Mutation (SORMAIN)
Intent —
Patients with acute myeloid leukemia ( AML) with internal tandem duplication mutation in the FMS-like tyrosine kinase 3 gene (FLT3-ITD) have a poor prognosis, often relapse, and die as a consequence of AML, despite undergoing allogeneic hematopoietic stem cell transplant (HCT). Whether a maintenance therapy using FLT3 inhibitors, such as the multitargeted tyrosine kinase inhibitor sorafenib, improves outcome after HCT, is currently uncertain.
MAINS
In a randomized , placebo-controlled, double-blind phase II trial (SORMAIN; German Clinical Trials Register: DRKS00000591), 83 adult patients with complete hematologic remission FLT3-ITD-positive AML after HCT were randomly assigned to receive either multitargeted sorafenib (n = 43) or placebo (n = 40 placebo) inhibitor FLT3-kinase for 24 months. A primary endpoint of this trial was Relapse-free Survival (RFS). The definition of Relapse was relapse or death, which happened first.
OUTCOMES
The hazard ratio (HR) for relapse or death in the sorafenib group versus the placebo group was 0.39 with a median follow-up of 41.8 months (95 percent CI, 0.18 to 0.85; log-rank P = .013). The 24-month RFS likelihood was 53.3% (95 % CI, 0.36 to 0.68) with placebo versus 85.0% (95 % CI, 0.70 to 0.93) with sorafenib (HR, 0.256; 95 % CI, 0.10 to 0.65; log-rank P = .002). Exploratory results indicate that patients with undetectable minimal residual disease (MRD) prior to HCT and those with observable MRD following HCT derive the greatest value from sorafenib.
CONCLUSION
Sorafenib maintenance therapy decreases risk for FLT3-ITD – positive AML relapse and death after HCT.