Reduced-toxicity conditioning regimen for older patients with AML: fludarabine plus treosulfan

Myeloablative conditioning regimen is associated with high non-relapse mortality (NRM) rates in older patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS).¹ Regimens which fuse the lower organ toxicity associated with reduced intensity conditioning and the antileukemic activity observed with myeloablative conditioning have been provisionally named as reduced toxicity conditioning regimens.¹ One promising reduced toxicity conditioning regimen is fludarabine + treosulfan (FluTreo).

Recently, Beelen et al.¹ published an observational comparative analysis of FluTreo vs fludarabine + (FluMel) or + (BuCy) in Bone Marrow Transplantation. Here, we summarize the key findings below.

Methods¹

• This was a retrospective European Society for Blood and Marrow Transplantation-registry based study.
• Data of patients from both the registry and the MC-FludT.14/L Trial II comparing FluTreo with FluBu (NCT00822393) was analyzed.
• A 1:1 propensity score matched analysis (PSA) was performed to reduce confounding due to differences between study and registry patients.
• The outcomes included a comparison of estimates of overall survival (OS), relapse incidence, and NRM within 2-years of transplant between the three conditioning regimens.

Key findings¹

• A total of 968 and 287 patients with AML and MDS, respectively were included
  • FluTreo (n = 174 and n = 78)
  • FluMel (n = 256 and n = 82)
  • BuCy (n = 503 and n = 127)

PSA outcome comparison in AML patients

• Figure 1 shows the 1:1 PSA for all three conditioning regimens.
• The 2-year NRM was lower for FluTreo vs FluMel in unpaired comparison (p = 0.019).
• The 2-year OS was higher for FluTreo vs FluMel in unpaired comparison (p = 0.04).

• The 2-year OS was higher for FluTreo vs BuCy and was significantly different in both paired (p < 0.001) and unpaired comparison (p < 0.001).

Figure 1. 1:1 PSA of clinical endpoints 2-years posttransplant for A FluTreo vs FluMel and B FluTreo vs BuCy*

BuCy, busulfan + cyclophosphamide; FluMel, fludarabine + melphalan; FluTreo, fludarabine + treosulfan; NRM, non-relapse mortality; OS, overall survival; PSA, propensity score matched analysis; RI, relapse incidence.
*Adapted from Beelen, et al.¹

PSA outcome comparison in MDS patients

• The 2-year NRM was lower for FluTreo vs BuCy in both paired and unpaired comparison (p = 0.13 and p = 0.18).
• The 2-year OS was higher for FluTreo vs BuCy in both paired and unpaired comparison (p = 0.01 each).

Multivariate comparison of outcomes

• For AML patients, multivariate analysis corroborated all significant results obtained by PSA for 2-year NRM and OS endpoints.
• For MDS patients, results of 2-year NRM and OS endpoints were also confirmed.
  • Only 2-year OS between FluTreo and BuCy regimens was significantly different.