Adding sirolimus to a standard graft-versus-host disease (GVHD) prophylaxis of mycophenolate mofetil (MMF) and cyclosporine (CSP) can significantly reduce the risks of grades II-IV and III-IV acute GVHD and non-relapse mortality (NRM), according to results of a phase 3 multi-center randomized trial presented at ASH.
The study analyzed unrelated donor hematopoietic cell transplant (HCT) outcomes of 158 patients (MMF/CSP, n=74; MMF/CSP/sirolimus, n=84) with a median age of 62 years (range, 18-79).
One-year overall survival (OS) was significantly higher in MMF/CSP/sirolimus arm compared to the MMF/CSP arm: 85% vs. 72%, respectively (p=0.03). Other outcomes are shown in the table below.
| Outcome | MMF/CSP | MMF/CSP/ sirolimus | p-value |
| 1-year OS | 72% | 85% | p=0.03 |
| 1-year PFS | 65% | 77% | p=0.08 |
| Day-100 acute II-IV GVHD | 53% | 25% | p=0.0001 |
| Day-100 acute III-IV GVHD | 8% | 2% | p=0.04 |
| 1-year chronic GVHD | 49% | 48% | p=0.94 |
| 1-year NRM | 15% | 5% | p=0.007 |
| 1-year relapse/progression | 21% | 19% | p=0.86 |
Lead author Dr. Brenda Sandmaier of the Fred Hutchinson Cancer Research Center noted in her oral presentation that because an interim analysis revealed that the sirolimus arm had significantly lower acute GVHD and improved survival than the standard MMF/CSP arm, the trial was closed early.
Because the triple prophylactic regimen also reduced non-relapse mortality without increasing the risk of relapse or progressive malignancy, the researchers recommended that the regimen be considered in the future as the standard of care in adults undergoing minimal-intensity unrelated donor HCT.