Long-term survival of sorafenib-treated FLT3-ITD-positive acute myeloid leukaemia patients relapsing after allogeneic stem cell transplantation

S K Metzelder; T Schroeder; M Lübbert; M Ditschkowski; K Götze; S Scholl; R G Meyer; P Dreger; N Basara; M F Fey; H R Salih; A Finck; T Pabst; A Giagounidis; G Kobbe; E Wollmer; J Finke; A Neubauer; A Burchert

doi:10.1016/j.ejca.2017.09.016

Long-term survival of sorafenib-treated FLT3-ITD-positive acute myeloid leukaemia patients relapsing after allogeneic stem cell transplantation

Eur J Cancer. 2017 Nov:86:233-239. doi: 10.1016/j.ejca.2017.09.016. Epub 2017 Oct 18.

Authors

S K Metzelder¹, T Schroeder², M Lübbert³, M Ditschkowski⁴, K Götze⁵, S Scholl⁶, R G Meyer⁷, P Dreger⁸, N Basara⁹, M F Fey¹⁰, H R Salih¹¹, A Finck³, T Pabst¹⁰, A Giagounidis¹², G Kobbe², E Wollmer¹, J Finke³, A Neubauer¹, A Burchert¹³

Affiliations

¹ Philipps Universität Marburg, Universitätsklinikum Gießen und Marburg, Standort Marburg, Klinik für Hämatologie, Onkologie und Immunologie, Marburg, Germany.
² University of Duesseldorf, Medical Faculty, Department of Hematology, Oncology and Clinical Immunology, Duesseldorf, Germany.
³ University of Freiburg, Department of Hematology/Oncology, Freiburg, Germany.
⁴ Department of Bone Marrow Transplantation, West German Cancer Center, University Hospital Essen, Germany.
⁵ Department of Internal Medicine III, Technische Universität München, Munich, Germany.
⁶ Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany.
⁷ St.-Johannes-Hospital Dortmund, Klinik für Innere Medizin II, Dortmund, Germany.
⁸ Department of Medicine, University of Heidelberg, Heidelberg, Germany.
⁹ Malteser Krankenhaus St. Franziskus-Hospital, Medizinische Klinik I, Flensburg, Germany.
¹⁰ Department of Medical Oncology, Inselspital and University of Bern, Bern, Switzerland.
¹¹ Department of Hematology/Oncology, Eberhard Karls-University, Tuebingen, Germany.
¹² Marien Hospital Düsseldorf, Klinik für Onkologie, Hämatologie und Palliativmedizin, Düsseldorf, Germany.
¹³ Philipps Universität Marburg, Universitätsklinikum Gießen und Marburg, Standort Marburg, Klinik für Hämatologie, Onkologie und Immunologie, Marburg, Germany. Electronic address: burchert@staff.uni-marburg.de.

PMID: 29055209
DOI: 10.1016/j.ejca.2017.09.016

Abstract

Background: Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia (AML) relapsing after allogeneic stem cell transplantation (allo-SCT) has a dismal prognosis with limited therapeutic options. FLT3-ITD kinase inhibition is a reasonable but palliative experimental treatment alternative in this situation. Information on long-term outcome is not available.

Methods: We performed a long-term follow-up analysis of a previously reported cohort of 29 FLT3-ITD-positive AML patients, which were treated in relapse after allo-SCT with sorafenib monotherapy.

Findings: With a median follow-up of 7.5 years, 6 of 29 patients (21%) are still alive. Excluding one patient who received a second allo-SCT, five patients (17%) achieved sustained complete remissions with sorafenib. Four of these patients are in treatment-free remission for a median of 4.4 years.

Interpretation: Sorafenib may enable cure of a proportion of very poor risk FLT3-ITD-positive AML relapsing after allo-SCT.

Keywords: Acute myeloid leukemia; FLT3-ITD; Hematopoietic stem cell transplantation; Sorafenib.

Publication types

Multicenter Study
Observational Study

MeSH terms

Adolescent
Adult
Aged
Antineoplastic Agents / adverse effects
Antineoplastic Agents / therapeutic use*
Biomarkers, Tumor / genetics*
Disease Progression
Disease-Free Survival
Female
Germany
Humans
Kaplan-Meier Estimate
Leukemia, Myeloid, Acute / enzymology
Leukemia, Myeloid, Acute / genetics
Leukemia, Myeloid, Acute / mortality
Leukemia, Myeloid, Acute / therapy*
Male
Middle Aged
Niacinamide / adverse effects
Niacinamide / analogs & derivatives*
Niacinamide / therapeutic use
Phenylurea Compounds / adverse effects
Phenylurea Compounds / therapeutic use*
Protein Kinase Inhibitors / adverse effects
Protein Kinase Inhibitors / therapeutic use*
Recurrence
Remission Induction
Retrospective Studies
Risk Factors
Sorafenib
Stem Cell Transplantation / adverse effects*
Tandem Repeat Sequences*
Time Factors
Transplantation, Homologous
Treatment Outcome
Young Adult
fms-Like Tyrosine Kinase 3 / genetics*

Substances

Antineoplastic Agents
Biomarkers, Tumor
Phenylurea Compounds
Protein Kinase Inhibitors
Niacinamide
Sorafenib
FLT3 protein, human
fms-Like Tyrosine Kinase 3