Allogeneic SCT After High versus Reduced-Intensity Conditioning in Patients with MDS or AML: Results of a Phase 3 BMT CTN 0901 Trial
The BMT CTN 0901 is a randomized phase 3 trial that compared outcomes by conditioning intensity, reduced-intensity conditioning (RIC) versus myeloablative conditioning (MAC) in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML); the results of this trial were reported by Scott and colleagues.1 A total of 272 patients were enrolled and were randomized to receive MAC (n = 135) or RIC (n = 137).The RIC regimens consisted of fludarabine with busulfan (Flu/Bu, n = 110) or melphalan (FM, n = 27); the MAC regimens were busulfan with cyclophosphamide (Bu/Cy, n = 40); or fludarabine (Bu/Flu, n = 87); or cyclophosphamide (120 mg/kg) and total body irradiation (CyTBI, n = 8). The majority of patients randomized to RIC received a busulfan-based regimen. The planned enrollment was 356 patients; however, based on recommendation of an independent Data Safety Monitoring Board review, accrual was stopped early due to a presumed benefit of the MAC regimen. The intent-to-treat analysis showed that the primary end point of overall survival (OS) at 18 months postrandomization was numerically higher for patients treated in the MAC arm (77.4% vs 67.7%) compared with RIC; however, the difference was not statistically significant (P = .07). However, in a subgroup analysis by disease group, patients with AML derived significant OS benefit with MAC versus RIC (76.8% vs 63%; P =.027). By disease and treatment, the 18-month relapse was significantly higher in patients who received RIC in both the AML (50% vs 16.5%; P <.01) and MDS (37% vs 3.7%) subgroups compared with the MAC arm. This translated to a significantly longer relapse-free survival (RFS) for patients in the MAC arm (68.8% vs 47.3%; difference of 20.4%; P <.01). Grade 2/4 acute graft-versus-host disease (GvHD) through 100 days was significantly higher with the MAC regimen (44.7% vs 31.6%; P = .024) compared with the RIC regimen, as were rates of chronic GvHD (64% vs 47.6%; P = .019). Treatment-related mortality (TRM) was significantly lower in the RIC arm (4.4% vs 15.8%; P = .02). The primary cause of death in both arms was relapse, with higher rates in the RIC arm (86% vs 32%). Based on these findings, the authors concluded that the MAC regimen remains the standard of care based on demonstrated RFS and OS benefit, although the RIC regimen was associated with higher rates of relapse and lower TRM.
- Scott BL, et al. ASH 2015. Abstract LBA8.