作者
Andreas Burchert,Gesine Bug,Lea Fritz,Jürgen Finke,Matthias Stelljes,Christoph Röllig,Ellen Wollmer,Ralph Wäsch,Martin Bornhäuser,Tobias Berg,Fabian Lang,Gerhard Ehninger,Hubert Serve,Robert Zeiser,Eva-Maria Wagner,Nicolaus Kröger,Christine Wolschke,Michael Schleuning,Katharina Götze,Christoph Schmid,Martina Crysandt,Eva Eßeling,Dominik Wolf,Ying Wang,Alexandra Böhm,Christian Thiede,Torsten Haferlach,Christian Michel,Wolfgang Bethge,Thomas Wündisch,Christian Brandts,Susanne Harnisch,Michael Wittenberg,Heinz-Gert Hoeffkes,Susanne Rospleszcz,Alexander Burchardt,Andreas Neubauer,M. Brügger,Konstantin Strauch,Carmen Schade‐Brittinger,Stephan Metzelder
摘要
PURPOSE Despite undergoing allogeneic hematopoietic stem cell transplantation (HCT), 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, frequently relapse, and die as a result of AML. It is currently unknown whether a maintenance therapy using FLT3 inhibitors, such as the multitargeted tyrosine kinase inhibitor sorafenib, improves outcome after HCT. PATIENTS AND METHODS In a randomized, placebo-controlled, double-blind phase II trial (SORMAIN; German Clinical Trials Register: DRKS00000591), 83 adult patients with FLT3-ITD–positive AML in complete hematologic remission after HCT were randomly assigned to receive for 24 months either the multitargeted and FLT3-kinase inhibitor sorafenib (n = 43) or placebo (n = 40 placebo). Relapse-free survival (RFS) was the primary endpoint of this trial. Relapse was defined as relapse or death, whatever occurred first. RESULTS With a median follow-up of 41.8 months, the hazard ratio (HR) for relapse or death in the sorafenib group versus placebo group was 0.39 (95% CI, 0.18 to 0.85; log-rank P = .013). The 24-month RFS probability 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 data show that patients with undetectable minimal residual disease (MRD) before HCT and those with detectable MRD after HCT derive the strongest benefit from sorafenib. CONCLUSION Sorafenib maintenance therapy reduces the risk of relapse and death after HCT for FLT3-ITD–positive AML.