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Real-world Study Confirms Clinical Benefit of Ruxolitinib in Heavily Pretreated cGVHD


A multicenter study supports the use of ruxolitinib in steroid-refractory and steroid-dependent chronic graft-versus-host disease, adding to promising clinical trial findings.

Clinical trial data suggests ruxolitinib is an effective second-line therapy for patients with chronic graft-versus-host disease (cGVHD) that is resistant to or dependent on corticosteroids, and a multicenter real-world study confirmed its benefits in heavily pretreated cGVHD patients.

An estimated 30% to 70% of patients who undergo allogeneic hematopoietic stem cell transplantation (HCT) are affected by cGVHD, an immune reaction that significantly impacts quality of life (QOL) and is a leading cause of treatment-related morbidity and non-relapse mortality following HCT. While a regimen of systemic corticosteroids with or without a calcineurin inhibitor is the standard of care for initial cGVHD treatment, approximately 50% to 60% of patients need second-line therapy or additional lines within 2 years of first-line corticosteroid initiation. This is largely due to being refractory to or dependent on steroids.

Following positive results in the randomized controlled REACH 3 trial (NCT03112603), ruxolitinib is becoming the go-to treatment for cGVHD after steroid failure, including dependence or refractoriness. Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, showed a 49.7% response rate after 24 weeks versus 25.6% in the best available therapy arm. It also showed better failure-free survival (FFS) than the best available therapy arm. FFS, a composite metric that factors in non-relapse mortality, primary hematologic malignancy relapse, and a switch of systemic cGVHD treatment, is a useful metric to evaluate shorter-term cGVHD treatment efficacy.

Even so, outcomes in real-world settings may not always align with those seen in clinical trials. The new study, published in Transplantation and Cellular Therapy, aimed to determine whether the FFS associated with ruxolitinib in clinical trial settings aligns with the FFS seen in heavily treated, steroid-refractory or dependent patients at 5 transplant centers.

The retrospective study included a total of 115 patients with cGVHD who were treated with ruxolitinib. More than half of the study cohort had severe cGVHD (60%), and the median age at ruxolitinib initiation was 57.5 years. Most patients (82%) received ruxolitinib in the fourth line of treatment or later, and the median follow-up duration was 13 months. About 70% of the patients were refractory to their latest line of treatment, while the rest had steroid-dependent cGVHD.

At 3, 6, and 12 months of ruxolitinib treatment, the overall response rate (ORR) was 48.6%, 54.9% and 48.5%. Mean daily doses of prednisone significantly tapered over time, with more than half of patients tapering to doses below 0.1 mg/kg per day by 12 months. Overall, 58.7%, 64.8% and 60.6% of patients experienced clinical benefit on ruxolitinib at 3, 6, and 12 months respectively. The clinical benefit metric was determined by combining ORR with steroid reduction rates.

At 12 months, OS was 83.3% and FFS was 64%. There were 39 failures (33.4%) overall, which most commonly included switching to another therapy due to resistance or intolerance, non-relapse mortality, and primary disease relapse. Patients with severe cGVHD at ruxolitinib initiation, a pre-transplant HCT-comorbidity index (CI) score of 3 or higher were at a higher risk of FFS due to an increasing risk of non-relapse mortality.

While the study was limited by its retrospective nature and therefore reliance on accuracy of medical records, the findings demonstrated that ruxolitinib had significant benefits for heavily treated patients in the real world. It also supports the use of FFS as an outcome measure in real-world studies of cGVHD therapies.


White J, Elemary M, Linn SM, et al. A multicenter, retrospective study evaluating clinical outcomes of ruxolitinib therapy in heavily pre-treated chronic GVHD patients with steroid-failure. Transplant Cell Ther. Published online November 30, 2022. doi:10.1016/j.jtct.2022.11.025

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