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| Ref Type | Journal Article | ||||||||||||
| PMID | (32673171) | ||||||||||||
| Authors | Burchert A, Bug G, Fritz LV, Finke J, Stelljes M, Röllig C, Wollmer E, Wäsch R, Bornhäuser M, Berg T, Lang F, Ehninger G, Serve H, Zeiser R, Wagner EM, Kröger N, Wolschke C, Schleuning M, Götze KS, 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 HG, Rospleszcz S, Burchardt A, Neubauer A, Brugger M, Strauch K, Schade-Brittinger C, Metzelder SK | ||||||||||||
| Title | Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3-Internal Tandem Duplication Mutation (SORMAIN). | ||||||||||||
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| Abstract Text | 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.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.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.Sorafenib maintenance therapy reduces the risk of relapse and death after HCT for FLT3-ITD-positive AML. | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Sorafenib | Phase II | Actionable | In a Phase II trial (SORMAIN), maintenance treatment with Nexavar (sorafenib) following hematopoietic stem cell transplantation in patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (n=43) resulted in a median relapse-free survival (RFS) that was not reached vs 30.9 mo in the placebo arm (n=40) at a median follow-up of 41.8 mo (HR=0.39, p=0.013), and the estimated probability of 24-mo RFS was 85.0% vs 53.3% (HR=0.255, p=0.002) (PMID: 32673171). | 32673171 |