Background
REACH2: phase III open-label randomized trial in 309 patients ≥12 years with glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation, comparing ruxolitinib with investigator's choice of best available therapy.
Interventions and follow up
Arm A: ruxolitinib 10 mg BID
Arm B: investigator's choice (ATG, extracorporeal photopheresis, mesenchymal stromal cells, low-dose methotrexate, mycophenolate mofetil, mTOR inhibitor, etanercept, or infliximab)
Primary endpoint: overall response at day 28
Key secondary endpoint: durable overall response at day 56
mFollow up: 5.04mo (Arm A), 3.58mo (Arm B)
Arm B: investigator's choice (ATG, extracorporeal photopheresis, mesenchymal stromal cells, low-dose methotrexate, mycophenolate mofetil, mTOR inhibitor, etanercept, or infliximab)
Primary endpoint: overall response at day 28
Key secondary endpoint: durable overall response at day 56
mFollow up: 5.04mo (Arm A), 3.58mo (Arm B)
Results
ORR at D28: 62% (96 pts) vs 39% (61 pts); OR 2.64, 95% CI 1.65–4.22, P<.001
Durable ORR at D56: 40% (61 pts) vs 22% (34 pts); OR 2.38, 95% CI 1.43–3.94, P<.001
Median failure-free survival: 5.0mo vs 1.0mo; HR 0.46, 95% CI 0.35–0.60
mOS: not sufficiently mature
Durable ORR at D56: 40% (61 pts) vs 22% (34 pts); OR 2.38, 95% CI 1.43–3.94, P<.001
Median failure-free survival: 5.0mo vs 1.0mo; HR 0.46, 95% CI 0.35–0.60
mOS: not sufficiently mature
Adverse events
Cytopenias at D28 (ruxolitinib vs control): thrombocytopenia 33% vs 18%; anemia 30% vs 28%
Infection: CMV infection 26% vs 21%; overall safety consistent with known ruxolitinib toxicity
Infection: CMV infection 26% vs 21%; overall safety consistent with known ruxolitinib toxicity
Conclusions
Ruxolitinib significantly improved overall response and failure-free survival vs best available therapy in glucocorticoid-refractory acute GVHD, at the cost of higher rates of thrombocytopenia and cytopenias.
Key Limitations
Open-label design; heterogeneous control arm with crossover permitted at day 28, limiting long-term and OS comparisons. Short follow-up; survival data immature.
Clinical Context
Supported FDA approval of ruxolitinib for steroid-refractory acute GVHD in patients ≥12 years. ASCO/ASTCT and ESMO/EBMT guidance endorse ruxolitinib as preferred therapy for steroid-refractory acute GVHD.
References