BMT CTN 1501

Background

Open-label, multicenter, randomized phase II trial (BMT CTN 1501) of 127 patients with standard-risk acute GVHD (defined by Minnesota GVHD Risk Score and Ann Arbor biomarker status), testing whether sirolimus could replace prednisone as initial therapy and spare steroid exposure.

Interventions and follow up

Arm A: Sirolimus as initial therapy (n=58)
Arm B: Prednisone as initial therapy (n=64)
Primary endpoint: Day 28 complete response/partial response (CR/PR) rate
mFollow up: NR

Results

Day 28 CR/PR: 64.8% (sirolimus) vs 73% (prednisone), similar
Day 28 CR/PR with prednisone ≤0.25 mg/kg/day: 66.7% vs 31.7%, P<.001 (favoring sirolimus)
Steroid-refractory aGVHD, DFS, relapse, NRM, OS: no significant differences detected

Adverse events

Sirolimus benefits: Reduced steroid exposure and hyperglycemia, fewer grade 2–3 infections, improved immunosuppression discontinuation, and better patient-reported quality of life
Sirolimus risk: Increased risk of thrombotic microangiopathy

Conclusions

For clinical- and biomarker-defined standard-risk acute GVHD, sirolimus demonstrated similar initial treatment efficacy to prednisone while sparing steroid exposure and associated toxicity and improving quality of life, without compromising long-term survival.

Key Limitations

Modest sample size (N=127) powered as an estimation phase II study rather than a definitive superiority trial, and restricted to a biomarker-defined standard-risk population.

Clinical Context

BMT CTN 1501 supports a biomarker-guided, steroid-sparing strategy for standard-risk acute GVHD, where sirolimus can serve as an alternative to upfront high-dose prednisone in selected patients. It complements parallel efforts to risk-stratify aGVHD therapy by the Minnesota score and MAGIC/Ann Arbor biomarkers, and reflects the broader move toward de-escalating steroid exposure given its infectious and metabolic toxicity. Confirmatory phase III data are not yet available.

References