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

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.

Fig. 1. Outcome comparison of FluTreo with FluMel or BuCy by propensity score 1:1 matched-pairs analysis of acute myeloid leukemia patients.

Comparison of cumulative incidence of non-relapse mortality between (a) FluTreo and FluMel (b) FluTreo and BuCy; comparison of overall survival between (c) FluTreo and FluMel (d) FluTreo and BuCy; non-relapse mortality curves represent cumulative incidence estimates with relapse as competing risk, overall survival curves represent product-limit estimates; p-values for comparisons of non-relapse mortality were calculated by Gray’s test, p-values for comparisons of overall survival were calculated by log-rank test; FluTreo Fludarabine/Treosulfan with a total dose of 30 g/m², FluMel Fludarabine/ Melphalan with a total dose of 140 mg/m²; BuCy Busulfan with a total dose of 12.8 mg/kg and Cyclophosphamide with a total dose of 120 mg/kg (all agents given intravenously).