Long-Term Follow up of BMT CTN 0901, a Randomized Phase III Trial Comparing Myeloablative (MAC) to Reduced Intensity Conditioning (RIC) Prior to Hematopoietic Cell Transplantation (HCT) for Acute Myeloid Leukemia (AML) or Myelodysplasia (MDS) (MAvRIC Trial)
Bart L. Scott
Abstract
BMT CTN 0901 enrolled patients with MDS (N=54) or AML (N=218) (median age of 55 years) who had < 5% marrow blasts by morphology prior to HCT. The most common RIC regimen was FluBu2 (81%) and the most common MAC regimen was FluBu4 (64%). The planned enrollment was 356 patients; however, accrual was stopped early (N=272) due to a marked imbalance of relapse rates. While MAC resulted in longer relapse-free survival (RFS) at 18 months, there were no survival differences between conditioning intensities (Scott BL et al, JCO 2017). Data on all enrolled patients reported to the CIBMTR were used to supplement clinical trial outcomes beyond 18 months. Here we present an updated clinical trial analysis with a median follow up of 50 months.Overall survival (OS) at 4 years was 65% and 49% for MAC and RIC (p=0.02), respectively. In multivariate analysis of overall mortality, the hazard ratio (HR) for death was 1.54 (95% Confidence Interval [CI] 1.07-2.20, p=0.02) for RIC compared to MAC. Other risk factors for mortality were protocol-defined high risk disease (HR 1.77) and age of ≥50 ys (HR 2.20). RFS rates at 4 years was 58% and 34% for MAC and RIC (p<0.001); the corresponding HR was 2.06 (95% CI 1.48-2.85, p<0.001) for RIC vs. MAC. Cumulative incidences of transplant-related mortality and relapse are shown in the figure. Subset analysis of MDS patients (n=54) were directionally similar to the overall analysis but not statistically significant, likely due to limited power. Post-HCT relapse survival among patients with AML was 24% and 26% for MAC and RIC (p=0.87) 3 years after leukemia relapse, respectively.Long term follow up of MAvRIC showed longer survival for MAC recipients. Thus, this trial confirms the importance of intensity for HCT; for patients eligible for either intensity regimen, MAC is the superior choice. BMT CTN 0901 enrolled patients with MDS (N=54) or AML (N=218) (median age of 55 years) who had < 5% marrow blasts by morphology prior to HCT. The most common RIC regimen was FluBu2 (81%) and the most common MAC regimen was FluBu4 (64%). The planned enrollment was 356 patients; however, accrual was stopped early (N=272) due to a marked imbalance of relapse rates. While MAC resulted in longer relapse-free survival (RFS) at 18 months, there were no survival differences between conditioning intensities (Scott BL et al, JCO 2017). Data on all enrolled patients reported to the CIBMTR were used to supplement clinical trial outcomes beyond 18 months. Here we present an updated clinical trial analysis with a median follow up of 50 months. Overall survival (OS) at 4 years was 65% and 49% for MAC and RIC (p=0.02), respectively. In multivariate analysis of overall mortality, the hazard ratio (HR) for death was 1.54 (95% Confidence Interval [CI] 1.07-2.20, p=0.02) for RIC compared to MAC. Other risk factors for mortality were protocol-defined high risk disease (HR 1.77) and age of ≥50 ys (HR 2.20). RFS rates at 4 years was 58% and 34% for MAC and RIC (p<0.001); the corresponding HR was 2.06 (95% CI 1.48-2.85, p<0.001) for RIC vs. MAC. Cumulative incidences of transplant-related mortality and relapse are shown in the figure. Subset analysis of MDS patients (n=54) were directionally similar to the overall analysis but not statistically significant, likely due to limited power. Post-HCT relapse survival among patients with AML was 24% and 26% for MAC and RIC (p=0.87) 3 years after leukemia relapse, respectively. Long term follow up of MAvRIC showed longer survival for MAC recipients. Thus, this trial confirms the importance of intensity for HCT; for patients eligible for either intensity regimen, MAC is the superior choice.