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661 Sorafenib As Maintenance Therapy Post Allogeneic Stem Cell Transplantation for FLT3-ITD Positive AML: Results from the Randomized, Double-Blind, Placebo-Controlled Multicentre Sormain TrialClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 613. Acute Myeloid Leukemia: Clinical Studies: Maintenance after Allogeneic Stem Cell Transplant and Management of Refractory/Relapsed AML
Hematology Disease Topics & Pathways:
Diseases, AML, Biological, Adult, Therapies, Study Population, Clinically relevant, Myeloid Malignancies, TKI
Monday, December 3, 2018: 10:30 AM
Seaport Ballroom F (Manchester Grand Hyatt San Diego)

Andreas Burchert, MD1, Gesine Bug2*, Jürgen Finke, MD3, Matthias Stelljes, MD4, Christoph Rollig, MD, MSC5*, Ralph Wäsch, MD6, Martin Bornhäuser, MD7*, Tobias Berg, MD 8, Fabian Lang, MD9*, Gerhard Ehninger, MD10, Hubert Serve, MD11, Robert Zeiser, MD12,13, Eva-Maria Wagner, MD14, Nicolaus Kroeger15, Christine Wolschke, MD16*, Michael Schleuning, MD17*, Ahmet Elmaagacli18*, Katharina S. Götze, MD19, Christoph Schmid, MD20*, Edgar Jost, MD21*, Dominik Wolf22,23, Alexandra Böhm, MD24*, Christian Thiede, MD25, Torsten Haferlach, MD26, Wolfgang Bethge, MD27*, Susanne Harnisch, Dipl. Humanbiol.28*, Michael Wittenberg, PhD29*, Susanne Rospleszcz30*, Andreas Neubauer, MD31, Markus Brugger30*, Konstantin Strauch, PhD30*, Carmen Schade-Brittinger29* and Stephan K Metzelder, MD32*

1Dep. of Internal Medicine, Hematologgy, Oncology and Immunology, Philips Univ. Marburg, Marburg, Hessen, Germany
2Department of Medicine II, Hematology and Oncology, University Hospital Frankfurt, Frankfurt, Germany
3Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University of Freiburg, Freiburg, Germany
4Dept. of Internal Medicine A, University of Muenster, Muenster, Germany
5Medical Department I, University Hospital, Dresden, Germany
6Department of Medicine I Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany
7Medical Clinic and Policlinic I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany
8Department of Medicine II, Hematology/Oncology, Goethe University, Großostheim, Bayern, Germany
9Department of Medicine II, Hematology/Oncology, Goethe University, Frankfurt, Germany
10Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
11Department of Medicine 2, Hematology/Oncology, University Hospital Frankfurt, Frankfurt am Main, Germany
12University Medical Center, Freiburg, Germany
13Department of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg Medical Center, Freiburg, Germany
14Department of Hematology, Medical Oncology, & Pneumology, III. med. Klinik, Mainz, Germany
15Department of Stem Cell Transplantation, University Hospital Eppendorf, Hamburg, Germany
16Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
17Deutsche Klinik fuer Diagnostik, Wiesbaden, Germany
18Department of Hematology and Oncology, Asklepios Klinik St. Georg, Hamburg, Germany
19Department of Medicine III, Technical University of Munich, Munich, Germany
20Department of Hematology and Oncology, Klinikum Augsburg, Augsburg, Germany
21Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen University, Aachen, Germany
22Department of Hematology and Oncology, Innsbruck Medical University, Innsbruck, Austria
23Department of Hematology, Oncology and Rheumatology, Center of Integrated Oncology Cologne Bonn, University Hospital of Bonn, Bonn, Germany
24Dep. of Hematology/Oncology/Stem Cell Transplantation, Ordensklinikum Linz Elisabethinen, Linz, Austria
25Internal Medicine I, University of Technics Dresden Medical Dept., Dresden, Germany
26MLL Munchner Leukamie Labor Gmbh, Munchen, Germany
27Department of Hematology and Oncology, University Hospital Tuebingen, Tuebingen, Germany
28Coordinating Center for Clinical Trials, Philipps-University of Marburg, Marburg, Germany
29Coordinating Center for Clinical Trials, Philipps University Marburg, Marburg, Germany
30Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Helmholtz Zentrum München, München, Germany
31Klinik für Innere Medizin, Schwerpunkt Hämatologie, Onkologie und Immunologie, Philipps University, Marburg, Germany
32Dep. of Internal Medicine, Hematology, Oncology and Immunology, Philipps University Marburg and University Hospital Giessen and Marburg, Campus Marburg, Marburg, Germany

Introduction: Most patients with FLT3-ITD-positive AML, who relapse after allogenic stem cell transplantation (allo-SCT) die from their disease. Whether prophylactic FLT3-ITD inhibition with sorafenib can prevent AML relapse and improve outcome of patients in complete hematological remission (CHR) after allo-SCT is unknown and was tested in the SORMAIN trial.

Methods: This randomized, double blind, placebo-controlled study was done at 14 centers in Germany and Austria. Patients with FLT3-ITD+ AML, aged 18 years or older, who had undergone allogenic stem cell transplantation from a HLA-matched sibling donor, 10/10 or 9/10 HLA-matched unrelated donor, and who were in confirmed CHR at the time of screening between day +30 and day +100 post allo-SCT, were included. Patients were randomly assigned (1:1) to receive either sorafenib (starting dose: 2 x 1 tbl. [2 x 200mg] qd, increasing every 14d to up to 2 x 2 tbl. [2 x 400mg] qd according to tolerability) or placebo (2 x 1 or 2 tbl. qd) for up to 24 months. Randomization was done centrally. In case of drug related adverse events, study medication could be interrupted, stepwise reduced to a minimum of 2 x 1 tbl. qd, temporarily withheld and recommenced at a lower dose level. FLT3-ITD diagnostics was done centrally at baseline and at time of relapse. In relapsing patients, off-label compassionate use of sorafenib was possible. The primary endpoint was relapse-free survival (RFS) as defined by either hematological relapse or death from any cause. The secondary endpoint was overall survival (OS). We here report the final RFS analysis. The OS results will be unblinded only prior to the ASH meeting and will be reported there. The SORMAIN study was terminated prior to full recruitment because of slow accrual. SORMAIN was registered with the European Clinical Trials Database (EudraCT 2010-018539-16) and the German Clinical Trials Register (DRKS00000591).

Results: Between October 29, 2010, and May 17, 2016, 83 patients (41 males, 42 females) were randomized and included in the primary analysis (placebo, n=40; sorafenib, n=43). Median age was 54 years (IQR 47.75 - 61.33) for the entire study population and not significantly different between sorafenib and placebo groups. With a median follow up of 41.8 months after randomization (IQR 24.1 – 42.5), median RFS was 30.9 months (lower bound of 95% CI 5.2 months) in the placebo group versus not reached in the sorafenib group, corresponding to a 2-year RFS of 53,3 % (95% CI 36.5-67.5) in the placebo versus 85.0 % (69.5-93.0) in the sorafenib group (hazard ratio [HR] 0.39, 95% CI; 0.18 -0.85; P=0.0135) (Fig. 1). Overall, sorafenib was well tolerated. The most common grade 3-4 adverse event in both groups was acute GvHD (seven [ 17.5%] in the placebo group vs. nine [20.9%] in the sorafenib group.

Conclusion: Sorafenib maintenance therapy after allo-SCT is feasible and significantly reduces the risk of relapse or death in patients with FLT3-ITD positive AML. OS results will be presented at the meeting.

Disclosures: Burchert: Bristol Myers Squibb: Honoraria, Research Funding; Bayer: Research Funding; Pfizer: Honoraria; AOP Orphan: Honoraria, Research Funding; Novartis: Research Funding. Bug: Amgen: Honoraria; Neovii: Other: Travel Grant; Novartis Pharma: Honoraria, Research Funding; Astellas Pharma: Other: Travel Grant; Jazz Pharmaceuticals: Other: Travel Grant; Celgene: Honoraria; Janssen: Other: Travel Grant. Finke: Medac: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding; Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding. Stelljes: Pfizer: Consultancy, Honoraria, Research Funding; MSD: Consultancy; JAZZ: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Rollig: Bayer: Research Funding; Janssen: Research Funding. Wäsch: Pfizer: Honoraria. Lang: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding. Ehninger: Cellex Gesellschaft fuer Zellgewinnung mbH: Employment, Equity Ownership; GEMoaB Monoclonals GmbH: Employment, Equity Ownership; Bayer: Research Funding. Serve: Bayer: Research Funding. Kroeger: Neovii: Honoraria, Research Funding; JAZZ: Honoraria; Sanofi: Honoraria; Celgene: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Götze: JAZZ Pharmaceuticals: Honoraria; Novartis: Honoraria; Takeda: Honoraria, Other: Travel aid ASH 2017; Celgene: Honoraria, Research Funding. Schmid: Jazz Pharma: Honoraria, Other: Travel grant, Speakers Bureau. Wolf: BMS: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria, Research Funding; AOP Orphan: Honoraria, Research Funding. Thiede: AgenDix: Other: Ownership; Novartis: Honoraria, Research Funding. Haferlach: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Bethge: Miltenyi Biotec GmbH: Consultancy, Honoraria, Research Funding; Neovii GmbH: Honoraria, Research Funding.

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