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Superior DFS and OS With FluMel vs FluBu in Older Patients With MDS
Orlando, Florida—A reduced-intensity conditioning (RIC) regimen for older patients with myelodysplastic syndromes (MDS) comprised of fludarabine plus melphalan (FluMel) is tied to superior disease-fee survival (DFS) and overall survival (OS) than fludarabine plus busulfan (FluBu) according to data that will be presented by Betul Oran, MD, MS, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas, MD Anderson Cancer Center, Houston, at the 2019 ASH Annual Meeting.
Citing several studies that have raised concerns about disease control when RIC is used in MDS, and a lack of consensus regarding the ideal conditioning regimen, Dr Oran and colleagues conducted a study of 1045 patients with MDS to compare the 2 most frequently used RIC regimens, FluBu and FluMel.
Patients in the study were aged ≥ 60 years and had their first HSCT with a matched related or unrelated donor using RIC (ie, a regimen incorporating IV busulfan ≤7.2 mg/kg or low-dose melphalan ≤150 mg/m2) between 2007 and 2016.
Ultimately, 697 patients received FluBu (busulfan 6.4 mg/kg, 87%; busulfan 3.2 mg/kg, 13%) and 448 received FluMel (melphalan 140 mg/m2, 80%; melphalan 100 mg/m2, 20%).
The FluBu and FluMel treatment arms were comparable vis-à-vis disease and transplant-related characteristics, and the hematopoietic CI was ³3 in 61% of FluBu recipients versus 59% of FluMel recipients. At hematopoietic CI, the MDS risk score was high or very high in 34% of patients in both treatment arms.
Compared with FluBu, the FluMel regimen was tied to a reduced relapse incidence after HSCT. Furthermore, the 1-year adjusted relapse incidence was 43% and 25% with FluBu and FluMel, respectively (P ≤.0001).
Alternatively, transplant-related mortality was found to be higher with FluMel versus FluBu (27% vs 15%, respectively; P ≤.0001). This difference endured at 2- and 3-years postHSCT.
Because FluMel led to a greater improvement in relapse incidence than FluBu did for the improvement of transplant-related mortality, DFS was improved at 1-year and beyond with FluMel versus FluBu (48% vs 41% at 1-year, respectively; P = .030, and 38% vs 28% at 3-years, respectively; P = .0030).
Notably, Dr Oran and co-investigators did not observe a higher incidence of severe grade 3-4 acute graft versus host disease (GVHD; HR, 1.2; 95% CI, 0.9-1.6; P = .3) or chronic GvHD (HR, 0.9; 95% CI, 0.7-1.06; P = .2) with FluMel. Grade 2-4 acute GVHD was observed more frequently in the FluMel versus FluBu arms, however (HR, 1.3; 95% CI, 1.1-1.6; P = .006).
According to the investigators, although this resulted in inferior GVHD-free, relapse-free survival outcomes within the first 2 months of therapy with FluMel (HR, 1.9; HR=1.4-2.6; P <.001), FluMel led to superior outcomes of GVHD-free, relapse-free survival >2 months versus FluBu (HR, 0.7; 95% CI, 0.6-0.8; P <.001).
“Our results suggest that between the two most commonly used RIC regimens in older MDS patients, FluMel was associated with superior DFS and overall survival compared with FluBu due to reduced RI [relapse incidence] despite higher [transplant-related mortality],” Dr Oran and colleagues conclude.—Hina Porcelli
Oran B, Ahn KW, Fretham C, et al. Fludarabine and melphalan compared with reduced doses of busulfan and flurabine improves transplant outcomes in older MDS patients. Presented at: the 2019 ASH Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 253.
