Patients who develop steroid-refractory acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic cell transplantation have poor prognosis, highlighting an unmet therapeutic need. In this open-label, phase 2 study ( identifier, NCT02953678), patients aged ≥12 years with grades II to IV steroid-refractory aGVHD were eligible to receive ruxolitinib orally starting at 5 mg twice daily plus corticosteroids until treatment failure, unacceptable toxicity, or death. The primary endpoint was overall response rate (ORR) at Day 28; the key secondary endpoint was duration of response (DOR) at 6 months. As of July 2, 2018, 71 patients received ≥1 dose of ruxolitinib. Forty-eight patients (67.6%) had grade III/IV aGVHD at enrollment. At Day 28, 39 patients (54.9% [95% CI, 42.7%-66.8%]) had an overall response, including 19 (26.8%) with complete responses. Best ORR at any time was 73.2% (complete response, 56.3%). Responses were observed across skin (61.1%), upper (45.5%) and lower (46.0%) gastrointestinal tract, and liver (26.7%). Median DOR was 345 days. Overall survival estimate at 6 months was 51.0%. At Day 28, 24/43 patients (55.8%) receiving ruxolitinib and corticosteroids had a ≥50% corticosteroid dose reduction from baseline. The most common treatment-emergent adverse events were anemia (64.8%), thrombocytopenia (62.0%), hypokalemia (49.3%), neutropenia (47.9%), and peripheral edema (45.1%). Ruxolitinib produced durable responses and encouraging survival compared with historical data in patients with steroid-refractory aGVHD who otherwise have dismal outcomes. The safety profile was consistent with expectations for ruxolitinib and this patient population.
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