Burchert, Andreas; Bug, Gesine; Fritz, Lea V; Finke, Jürgen; Stelljes, Matthias; Röllig, Christoph; Wollmer, Ellen; Wäsch, Ralph; Bornhäuser, Martin; Berg, Tobias; Lang, Fabian; Ehninger, Gerhard; Serve, Hubert; Zeiser, Robert; Wagner, Eva-Maria; Kröger, Nicolaus; Wolschke, Christine; Schleuning, Michael; Götze, Katharina S; Schmid, Christoph; Crysandt, Martina; Eßeling, Eva; Wolf, Dominik; Wang, Ying; Böhm, Alexandra; Thiede, Christian; Haferlach, Torsten; Michel, Christian; Bethge, Wolfgang; Wündisch, Thomas; Brandts, Christian; Harnisch, Susanne; Wittenberg, Michael; Hoeffkes, Heinz-Gert; Rospleszcz, Susanne; Burchardt, Alexander; Neubauer, Andreas; Brugger, Markus; Strauch, Konstantin; Schade-Brittinger, Carmen; Metzelder, Stephan K     «

Burchert, Andreas; Bug, Gesine; Fritz, Lea V; Finke, Jürgen; Stelljes, Matthias; Röllig, Christoph; Wollmer, Ellen; Wäsch, Ralph; Bornhäuser, Martin; Berg, Tobias; Lang, Fabian; Ehninger, Gerhard; Serve, Hubert; Zeiser, Robert; Wagner, Eva-Maria; Kröger, Nicolaus; Wolschke, Christine; Schleuning, Michael; Götze, Katharina S; Schmid, Christoph; Crysandt, Martina; Eßeling, Eva; Wolf, Dominik; Wang, Ying; Böhm, Alexandra; Thiede, Christian; Haferlach, Torsten; Michel, Christian; Bethge, Wolfgang; W...     »

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.      «

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, p...     »