Fludarabine-treosulfan versus fludarabine-melphalan or busulfan-cyclophosphamide conditioning in older AML or MDS patients - A clinical trial to registry data comparison.

Donal P McLornan, Dietrich Wilhelm Beelen, Péter Reményi, Eva-Maria Wagner-Drouet, Friedrich Stölzel, Simona Iacobelli, Peter Dreger, Mohamad Mohty, Matthias Stelljes, Wolfgang Bethge, Miroslaw Markiewicz, Fabio Ciceri, Linda Koster, Dirk-Jan Eikema, Anja van Biezen, Ibrahim Yakoub-Agha

Journal: Bone marrow transplantation 2024;59(5):670-679

PMID: 38383713

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Abstract

A randomized study (acronym: MC-FludT.14/L Trial II) demonstrated that fludarabine plus treosulfan (30 g/m²) was an effective and well tolerated conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT) in older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). To further evaluate this regimen, all 252 study patients aged 50 to 70 years were compared with similar patients, who underwent allo-HCT after fludarabine/melphalan (140 mg/m²) (FluMel) or busulfan (12.8 mg/kg)/cyclophosphamide (120 mg/kg) (BuCy) regimens and whose data was provided by the European Society for Blood and Marrow Transplantation registry. In 1:1 propensity-score matched-paired analysis (PSA) of AML patients, there was no difference in 2-year-relapse-incidence after FluTreo compared with either FluMel (n = 110, p = 0.28) or BuCy (n = 78, p = 0.98). However, 2-year-non-relapse-mortality (NRM) was lower compared with FluMel (p = 0.019) and BuCy (p < 0.001). Consequently, 2-year-overall-survival (OS) after FluTreo was higher compared with FluMel (p = 0.04) and BuCy (p < 0.001). For MDS patients, no endpoint differences between FluTreo and FluMel (n = 30) were evident, whereas 2-year-OS after FluTreo was higher compared with BuCy (n = 25, p = 0.01) due to lower 2-year-NRM. Multivariate sensitivity analysis confirmed all significant results of PSA. Consequently, FluTreo (30 g/m²) seems to retain efficacy compared with FluMel and BuCy, but is better tolerated by older patients.

Address: Department of Haematology and Stem Cell Transplantation, West German Cancer Center, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany. [email protected].; Department of Biology, University Tor Vergata of Rome, Rome, Italy.; EBMT Data Office Leiden, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, Netherlands.; Division of Stem Cell Transplantation and Cellular Immunotherapies, Department of Internal Medicine 2, University Hospital Schleswig-Holstein, Kiel, Kiel University, Kiel, Germany.; Faculty of Medicine Carl Gustav Carus Dresden, Technical University Dresden, Dresden, Germany.; Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Department of Hematology and Oncology, University Hospital Tübingen, Tübingen, Germany.; Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.; Third Department of Medicine - Hematology, Internal Oncology & Pneumology, Johannes Gutenberg-University Medical Center, Mainz, Germany.; St. István and St. László Hospital of Budapest, Budapest, Hungary.; Department of Medicine A, Hematology, Oncology, Hemostaseology and Pneumology, University Hospital Münster, Münster, Germany.; Department of Hematology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow, Rzeszow, Poland.; University College London Hospital, London, UK.; Centre Hospitalier Universitaire de Lille, Université Lille, INSERM U1286, Infinite, Lille, France.; Hospital Saint-Antoine, Sorbonne Université, Centre de Recherche Saint-Antoine (CRSA), Paris, France.

DOI: 10.1038/s41409-024-02241-2