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).

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.

Key learnings

FluTreo shows similar antileukemic activity vs FluMel. In addition, FluTreo is associated with better tolerability. Comparison between FluTreo and BuCy shows FluTreo is associated with lower NRM. This translated into improved OS. Overall, the results support FluTreo to be considered a reduced-toxicity conditioning regimen that achieves a similar efficacy compared to medium or high intensity regimens.