Originally published by 2 Minute Medicine^® (view original article). Reused on AccessMedicine with permission.

1. Ruxolitinib was shown to significantly improve failure-free survival for glucocorticoid-refractory chronic graft-versus-host disease (GVHD) compared to control therapy.

2. The incidence of thrombocytopenia and anemia was more common in patients treated with ruxolitinib.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

Allogeneic stem-cell transplantation is a life-saving therapy for various hematologic conditions. However, chronic GVHD is a serious complication that impairs its success and patients’ quality of life. Although glucocorticoids are the standard treatment for GVHD, approximately 50% of patients become refractory or dependent. Ruxolitinib, a Janus kinase 1 and 2 (JAK1/2) inhibitor, has been shown to be effective for GVHD in retrospective clinical studies. As such, this study examined the efficacy of ruxolitinib in treating chronic glucocorticoid-refractory and glucocorticoid-dependent GVHD. The study determined ruxolitinib resulted in a higher overall responses rate and more symptom reduction than control therapy. The study was limited by the open-label study design, which was needed to accommodate the various control-therapy options. Nonetheless, the study’s results were significant as a ruxolitinib treatment showed significantly greater disease response and symptom reduction compared to the control therapies.

Clicker to read the study in NEJM

Relevant Reading: Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease

In-Depth [randomized controlled trial]:

This multi-center randomized open-label controlled trial enrolled 329 patients from 149 centers in 28 countries. Patients who were at least 12 years old, diagnosed with glucocorticoid-refractory or glucocorticoid-dependent GVHD, previously underwent allogeneic stem-cell transplantation, and had previously responded to JAK inhibitors for acute GVHD were included in the study. Patients were excluded if they had received two or more systemic therapies for chronic GVHD alongside glucocorticoids. Patients were randomized in a 1:1 ratio to receive either ruxolitinib or control therapy defined as second-line treatments such as extracorporeal photopheresis, mycophenolate mofetil, or ibrutinib, respectively. The primary endpoint is the overall response, which consists of complete and partial responses at week 24. Notably, 82 patients (49.7%) discontinued ruxolitinib, 122 (74.4%) discontinued control therapy, and 61 (37.2%) crossed over from control therapy to ruxolitinib. Ruxolitinib resulted in higher overall response at 24 weeks (82 patients, 49.7%) compared to the control therapy (42 patients, 25.6%) (odds ratio [OR], 2.99; 95% confidence interval [CI], 1.44 to 2.60; risk ratio [RR], 1.93; 95% CI, 1.44 to 2.60; P<0.001). Additionally, patients are given ruxolitinib had longer failure-free survival (median failure-free survival, >18.6 months) than those on control therapy (median failure-free survival, 5.7 months) (hazard ratio, 0.37; 95% CI, 0.27 to 0.51; P<0.001). The probability of failure-free survival at 6 months was also higher in the ruxolitinib group (74.9%; 95% CI, 67.5 to 80.9) than control (44.5%; 95% CI, 36.5 to 52.1). Ruxolitinib-treated patients experienced higher rates of thrombocytopenia (15.2% vs. 10.1%), anemia (12.7% vs. 7.6%), and neutropenia (8.5% vs. 3.8%) than those given control therapy. The study noted longer follow-up than used in the current study would be necessary to demonstrate the impact ruxolitinib has on survival. Overall, this trial provided robust evidence for ruxolitinib treatment in the management of chronic glucocorticoid-refractory GVHD.

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