Examining the feasibility of clinical- and biomarker-based risk-adapted therapy for acute graft-versus-host disease (GVHD), a recent randomized phase II trial of the Blood and Marrow Transplant Clinical Trials Network, study 1501, revealed similar complete response/partial response (CR/PR) rates using sirolimus, a steroid-free option, compared to current standard of care, prednisone.
The trial included previously untreated pediatric and adult patients with Minnesota standard risk (MN-SR) acute GVHD with similar organ staging. The primary analysis included 122 patients with centrally assessed Ann Arbor (AA) 1 or 2 biomarker status randomized 1:1 to sirolimus (n=58) and prednisone (n=64).
Among the enrolled subjects, at day 28, sirolimus produced comparable CR/PR rates vs. 2mg/kg/day prednisone, with an improved CR/PR rate with prednisone ≤ 0.25mg/kg/day (66.7% vs. 33.3%, p < 0.001). Patients who received sirolimus achieved similar six-month disease-free survival with no evidence of excess grade 3-5 adverse events, infections, or steroid-refractory acute GVHD. (See chart below.)
MN-SR AA1/2 | Sirolimus | Prednisone | P value* |
| Day 28 CR/PR | 64.8% | 73% | 0.68 |
| Day 28 NR | 35% | 27% | |
| Day 56 CR/PR | 64.2% (95% CI 50.8% - 77.5%) | 79.4% (95% CI 69.1% - 89.6%) | 0.07 |
| Day 56 NR | 36% | 21% | |
| 6-month disease-free survival | 72.8% (95% CI 58.9 - 82.6%) | 78.1% (95% CI 65.9% - 88.4%) | NA |
CR=Complete Response; PR=Partial Response; NR=No Response; CI=Cumulative Incidence; NA=Not Available.
The findings of this multi-center, open-label trial were presented at the 2019 Transplantation & Cellular Therapy (TCT) Meetings of American Society for Transplantation and Cellular Therapy & CIBMTR®. Joseph Pidala, M.D., Ph.D., from the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., concluded that initial risk stratification with central biomarker assessment is possible. Prospectively, sirolimus produced durable CR/PR rates without the need for steroid therapy. Additional long-term analyses are planned with patient-reported outcomes data.
Pidala JA, et al., Bio Blood Marrow Transplant