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Burchert, A.* ; Bug, G.* ; Fritz, L.V.* ; Finke, J.* ; Stelljes, M.* ; Röllig, C.* ; Wollmer, E.* ; Wäsch, R.* ; Bornhäuser, M.* ; Berg, T.* ; Lang, F.* ; Ehninger, G.* ; Serve, H.* ; Zeiser, R.* ; Wagner, E.M.* ; Kröger, N.* ; Wolschke, C.* ; Schleuning, M.* ; Götze, K.S.* ; Schmid, C.* ; Crysandt, M.* ; Eßeling, E.* ; Wolf, D.* ; Wang, Y.* ; Böhm, A.* ; Thiede, C.* ; Haferlach, T.* ; Michel, C.* ; Bethge, W.* ; Wündisch, T.* ; Brandts, C.* ; Harnisch, S.* ; Wittenberg, M.* ; Hoeffkes, H.G.* ; Rospleszcz, S. ; Burchardt, A.* ; Neubauer, A.* ; Brugger, M. ; Strauch, K. ; Schade-Brittinger, C.* ; Metzelder, S.K.*

Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3-internal tandem duplication mutation (SORMAIN).

J. Clin. Oncol. 38, 2993-3002 (2020)
Verlagsversion DOI
Free by publisher
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 METHODSIn 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Minimal Residual Disease; Versus-host-disease; Flt3 Gene; Therapeutic Target; Younger Adults; Aml; Chemotherapy; Multicenter; Proliferation; Inhibition
ISSN (print) / ISBN 0732-183X
e-ISSN 1527-7755
Quellenangaben Band: 38, Heft: 26, Seiten: 2993-3002 Artikelnummer: , Supplement: ,
Verlag American Society of Clinical Oncology
Verlagsort 2318 Mill Road, Ste 800, Alexandria, Va 22314 Usa
Begutachtungsstatus Peer reviewed
Förderungen German Carreras Leukemia Foundation
Deutsche Forschungsgemeinschaft (DFG)