REACH 3 Trial

Background

REACH3: phase III open-label randomized trial in 329 patients ≥12 years with moderate or severe glucocorticoid-refractory or -dependent chronic GVHD, 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 (extracorporeal photopheresis, low-dose methotrexate, mycophenolate mofetil, mTOR inhibitor, infliximab, rituximab, pentostatin, imatinib, or ibrutinib)
Primary endpoint: overall response at week 24
Key secondary endpoint: failure-free survival
mFollow up: 57.3 weeks

Results

ORR at week 24: 49.7% vs 25.6%; OR 2.99, P<.001
Median failure-free survival: >18.6mo vs 5.7mo; HR 0.37, 95% CI 0.27–0.51, P<.001
Symptom response (mLSS): 24.2% vs 11.0%; OR 2.62, P=.001

Adverse events

Grade ≥3 cytopenias (ruxolitinib vs control): thrombocytopenia 15.2% vs 10.1%; anemia 12.7% vs 7.6%
Infection: similar rates of CMV infection between arms

Conclusions

Ruxolitinib significantly improved overall response, failure-free survival, and symptom response vs best available therapy in glucocorticoid-refractory or -dependent chronic GVHD, with higher rates of thrombocytopenia and anemia.

Key Limitations

Open-label design; heterogeneous control arm with crossover permitted at week 24, limiting durability and survival comparisons. Patient-reported symptom response was modest in both arms.

Clinical Context

Supported FDA approval of ruxolitinib for chronic GVHD after failure of one or two lines of systemic therapy. ASCO/ASTCT and ESMO/EBMT guidance endorse ruxolitinib for steroid-refractory chronic GVHD.

References