Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3-Internal Tandem Duplication Mutation (SORMAIN).

Abstract

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.

• Authors: Andreas Burchert, Gesine Bug, Lea V 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 S 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, Markus Brugger, Konstantin Strauch, Carmen Schade-Brittinger, Stephan K Metzelder
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 38 Issue 26 Pg. 2993-3002 (09 10 2020) ISSN: 1527-7755 [Electronic] United States
• PMID: 32673171 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Sorafenib
• FLT3 protein, human
• fms-Like Tyrosine Kinase 3

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Agents (adverse effects, therapeutic use)
• Chemotherapy, Adjuvant
• Double-Blind Method
• Female
• Germany
• Hematopoietic Stem Cell Transplantation (adverse effects, mortality)
• Humans
• Leukemia, Myeloid, Acute (enzymology, genetics, mortality, therapy)
• Maintenance Chemotherapy
• Male
• Middle Aged
• Mutation
• Neoplasm, Residual
• Protein Kinase Inhibitors (adverse effects, therapeutic use)
• Recurrence
• Sorafenib (adverse effects, therapeutic use)
• Tandem Repeat Sequences
• Time Factors
• Transplantation, Homologous
• Treatment Outcome
• Young Adult
• fms-Like Tyrosine Kinase 3 (genetics)