Ruxolitinib Active, Well-Tolerated in Patients With Steroid-Refractory Acute GVHD

In a phase 2 clinical trial, ruxolitinib was well-tolerated and led to responses in >50% of patients with steroid-refractory acute graft-versus-host disease (aGVHD; Blood. 2020 May 14;135[20]:1739-1749).

“Patients who develop steroid-refractory [aGVHD] after allogeneic hematopoietic cell transplantation have poor prognosis, highlighting an unmet therapeutic need,” wrote Madan H. Jagasia, MD, MBBS, MS, MMHC, Vanderbilt University Medical Center, Nashville, Tennessee, and co-investigators, who conducted the open-label study.

Patients were eligible for enrollment in the trial if they were aged ≥12 years and had grades II to IV steroid-refractory aGVHD. Participants would be given ruxolitinib starting at a dose of 5 mg twice daily plus corticosteroids, until treatment failure, unacceptable toxicity, or death occurred.

The main end point was overall response rate (ORR) at day 28, and a key secondary end point was 6-month duration of response (DOR).

Overall, 71 patients were enrolled in the trial and given at least 1 dose of ruxolitinib; 48 (67.6%) had grade III/IV aGVHD at baseline.

By day 28, a total of 39 (54.9%) patients had overall responses (95% CI, 42.7%-66.8%), including 19 (26.8%) complete responses. At any point in time, the best ORR was 73.2% (complete response, 56.3%), and Dr Jagasia et al observed responses across skin (61.1%), upper (45.5%) and lower (46.0%) gastrointestinal tract, and liver (26.7%).

The DOR was a median of 345 days, and the estimated rate of 6-month overall survival was 51.0%.

Among 43 patients receiving ruxolitinib and corticosteroids, 24 (55.8%) had a ≥50% corticosteroid dose reduction from baseline.

Anemia (64.8%), thrombocytopenia (62.0%), hypokalemia (49.3%), neutropenia (47.9%), and peripheral edema (45.1%) were the most frequently reported treatment-emergent adverse events.

“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,” Dr Jagasia and colleagues concluded.—Hina M. Porcelli