Journal Article Ahead of print
PubMed: 42610785 DOI: 10.1111/bjh.70735
Treatment sequence with gilteritinib and allogeneic haematopoietic stem cell transplantation in relapsed/refractory FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukaemia patients: A multicentre real-world study.
Br J Haematol
Authors: Desiree Kunadt, Sven Zukunft, Christoph Röllig, Stephan Metzelder, Andreas Burchert, Eva Wagner-Drouet, Oliver Kriege, Christoph Schliemann, Matthias Stelljes, Julian Ronnacker, Wolfgang Bethge, Jan Frederic Weller, Björn Steffen, Gesine Bug, Khouloud Kouidri, Claudia Baldus, Lars Fransecky, Elisa Sala, Uwe Platzbecker, Klaus Metzeler, Sabine Kayser, Inken Hilgendorf, Andreas Hochhaus, Tim H Brümmendorf, Edgar Jost, Anna Dorottya Doleschall, Thomas Schroeder, Jennifer Kaivers, Lambros Kordelas, Udo Holtick, Julia M Unglaub, Tim Sauer, Paul Sebastian Jäger, Guido Kobbe, Elena Stauffer, Johanna Tischer, Tobias Herold, Normann Steiner, David Nachbaur, Nicolaus Kröger, Jochen J Frietsch, Sabrina Kraus, Hermann Einsele, Mathias Hänel, Judith Schaffrath, William Krüger, Anne Brandenburg, Tobias A W Holderried, Laura Reinhardt, Markus Maulhardt … and 5 other authors
Affiliations
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, TU Dresden, Dresden, Germany.
- Department of Internal Medicine, Hematology, Oncology and Immunology, Philipps University Marburg and University Hospital Gießen and Marburg, Marburg, Germany.
- Department of Hematology, Oncology and Pneumology, University Medical Center Mainz, Mainz, Germany.
- Medizinische Klinik A, Universitätsklinikum Münster, Münster, Germany.
- Department for Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
- University Hospital Eppendorf, Hamburg, Germany.
- Medizinische Klinik 2, Hämatologie/Onkologie, Goethe-Universität, Frankfurt am Main, Germany.
- Klinik für Innere Medizin II, Universitätsklinikum Schleswig-Holstein, Kiel, Germany.
- Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany.
- Department of Hematology, Cell Therapy, Hemostaseology and Infectious Diseases, University Hospital Leipzig, Leipzig, Germany.
- Medical Faculty Mannheim, Institute of Transfusion Medicine and Immunology, Heidelberg University, German Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany.
- NCT Trial Center, National Center of Tumor Diseases, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany.
- Medizinische Klinik IV, Uniklinik RWTH Aachen, Aachen, Germany.
- Klinik für Hämatologie, Universitätsklinikum Essen, Essen, Germany.
- Department I of Internal Medicine, Medical Faculty and University Hospital, Cologne, University of Cologne, Cologne, Germany.
- Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
- Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Duesseldorf, Germany.
- Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
- Department of Hematology, Oncology, and Stem-Cell Transplantation, Munich Hospital Bogenhausen, Munich Municipal Hospital Group, Munich, Germany.
- Division of Hematology and Medical Oncology, Department of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Austria.
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
- Medizinische Klinik III, Klinikum Chemnitz, Chemnitz, Germany.
- Department of Hematology/Oncology, Martin Luther University Halle/Wittenberg, Halle, Germany.
- Clinic for Internal Medicine C-Haematology and Oncology, Stem Cell Transplantation and Palliative Care, University Medicine Greifswald, Greifswald, Germany.
- Medical Clinic and Polyclinic III Internal Medicine With a Focus on Oncology, Hematology, and Rheumatology, University Hospital Bonn, University of Bonn, Bonn, Germany.
- Division of Hematology, Medical University of Graz, Graz, Austria.
- Department of Hematology, Oncology, and Stem Cell Transplantation, Freiburg University Medical Center, Freiburg, Germany.
- Department of Hematology and Medical Oncology, University Medicine Göttingen, Göttingen, Germany.
Abstract
Patients with relapsed or refractory acute myeloid leukaemia (r/r AML) harbouring FMS-like tyrosine kinase 3 (FLT3) mutations generally have poor prognosis and limited treatment options. The second-generation FLT3 inhibitor gilteritinib provides better disease control compared to standard relapse therapies and was approved based on two randomized trials. We analysed its efficacy and safety in a real-world cohort of r/r AML patients undergoing gilteritinib treatment including allogeneic haematopoietic stem cell transplantation (alloHSCT). Data were collected from all consecutive r/r AML patients with FLT3-internal tandem duplication and/or FLT3-tyrosine kinase domain mutations receiving gilteritinib at 25 centres. Response and survival were analysed using descriptive and correlative statistics. A total of 156 patients were analysed, 55.1% with relapse after previous alloHSCT, and 46.2% with prior FLT3 inhibitor exposure. The overall complete remission/incomplete remission (CR/Cri) rate was 45.3%, with a median overall survival (OS) of 10.0 months. Patients receiving gilteritinib only had a 1-year OS of 34%, while those with consolidating alloHSCT had a 1-year OS of 76%-92%, depending on gilteritinib maintenance post-transplant. Resuming gilteritinib post-transplant led to an 85.7% CR/CRi rate. Our real-world data confirm that gilteritinib is an effective single-agent therapy for r/r AML with FLT3 mutations, with best outcomes when used as a bridge to transplant and post-transplant maintenance.
MeSH
Cells, Fms-Like Tyrosine Kinase 3, Microscopy, Electron, Scanning Transmission, Stem Cells, Maintenance, Protein-Tyrosine Kinases, Transplants, Tyrosine, Therapeutics, Cell Transplantation, Stem Cell Transplantation, Vascular Endothelial Growth Factor Receptor-1, Mutation, Transplantation