Background
Open-label, multicenter, single-arm phase II registrational study of 71 patients aged ≥12 years with grades II–IV steroid-refractory acute graft-versus-host disease, a population with poor prognosis and unmet therapeutic need. Conducted across 26 US centers.
Interventions and follow up
Regimen: Ruxolitinib orally, starting 5 mg twice daily, plus corticosteroids, until treatment failure, unacceptable toxicity, or death
Primary endpoint: Overall response rate (ORR) at day 28
Key secondary endpoint: Duration of response at 6 months
mFollow up: NR
Primary endpoint: Overall response rate (ORR) at day 28
Key secondary endpoint: Duration of response at 6 months
mFollow up: NR
Results
Day 28 ORR: 54.9% (95% CI 42.7–66.8), including 26.8% complete responses
Best ORR (any time): 73.2% (complete response 56.3%)
Median duration of response: 345 days
6-month OS: 51.0%
Best ORR (any time): 73.2% (complete response 56.3%)
Median duration of response: 345 days
6-month OS: 51.0%
Adverse events
Hematologic: Anemia 64.8%, thrombocytopenia 62.0%, neutropenia 47.9%
Metabolic/other: Hypokalemia 49.3%, peripheral edema 45.1%; overall safety profile consistent with expectations for ruxolitinib in this population
Metabolic/other: Hypokalemia 49.3%, peripheral edema 45.1%; overall safety profile consistent with expectations for ruxolitinib in this population
Conclusions
Ruxolitinib produced durable responses and encouraging survival in steroid-refractory acute GVHD, supporting its FDA approval as the first agent indicated for this otherwise dismal-prognosis population.
Key Limitations
Single-arm, non-randomized design with no concurrent comparator, limiting attribution of benefit to ruxolitinib versus continued steroids. Modest sample size (N=71). Cytopenias (anemia, thrombocytopenia, neutropenia) are frequent and overlap with GVHD- and transplant-related marrow suppression, complicating dosing. Definitive efficacy was established only in the subsequent randomized REACH2 trial.
Clinical Context
REACH1 was the registrational study supporting the 2019 FDA approval of ruxolitinib for steroid-refractory acute GVHD, the first drug approved in this setting; the subsequent randomized REACH2 trial (Zeiser NEJM 2020) confirmed its superiority over best available therapy. Ruxolitinib is now a standard option for steroid-refractory acute GVHD and, following REACH3, for steroid-refractory chronic GVHD.