Analysis of ruxolitinib as salvage therapy in patients with chronic graft-versus-host disease

Corticosteroids are the accepted first-line therapy for chronic graft-versus-host disease (cGvHD), a major complication of hematopoietic stem cell transplantation (HSCT). Nevertheless, 50–60% of these patients develop steroid-refractory GvHD (SR-GvHD), which is associated with poor survival rates. In order to improve patient outcomes, new second-line therapy options are required.

Badri Modi from Department of Surgery, Division of Dermatology, City of Hope, Duarte, CA, USA, and colleagues retrospectively evaluated patients with GvHD treated with ruxolitinib as salvage therapy. The study was published ahead of print in Biology of Blood and Marrow Transplantation.

Patients and methods

• N = 46 patients
• Median age = 49 years (range, 21–77)
• Follow-up duration: March 2016 – February 2018
• Patients received HSCT between July 1994 and April 2015
• GvHD
  • GvHD severity: 35 patients had severe and 8 patients moderate disease
  • Organ involvement: 63% (n=29) of cases had severe skin disease, the oral cavity was involved in 32.6% (n=15) of patients, eyes in 47.8% (n=22) of patients, lungs in 21.7% (n=10) of cases, and joints/fascia in 47.8% (n=22) of patients
• Study endpoints: organ specific responses, mean prednisone dose, as well as probability of ruxolitinib’s treatment failure-free survival (FFS), defined as absence of initiating additional systemic therapy, relapsed malignancy, medication intolerance, or death

Key findings

At 6 months of ruxolitinib therapy:

• Complete response (CR) rate: 10% (n=5)
• Partial response (PR) rate: 37% (n=17)
• Stable disease: 15% (n=7)

At 12 months of ruxolitinib therapy:

• Overall response rate (ORR): 43.4%
  • CR: 13% (n=6)
  • PR: 30% (n=14)
  • Stable disease: 15% (n=5)
• Organ response:
  • 25% (n=10) of patients with skin involvement
  • 60% (n=15) of patients with mouth involvement
  • 26% (n=23) of patients with eyes involvement
  • 10% (n=1) of patients with lung involvement
  • 41% (n=23) of patients with joints / fascia involvement
• Treatment failure: 45.7% of patients (n=21)
• FFS: 54.2% (95% CI, 0.388–0.673)
• Ruxolitinib use significantly associated with lower prednisone dose at 1 year compared to the baseline dose
• 52% of patients developed infections which led to higher overall mortality rates

In summary, the results of this study showed that ruxolitinib salvage therapy demonstrated a superior FFS and ORR at 12 months. It is also encouraging to note that ruxolitinib use led to lower steroid use. The authors stated that “ruxolitinib as salvage therapy is promising for cGvHD refractory to steroids.” The REACH3 phase III multicenter, open-label randomized trial (n = 324 patients) is underway to evaluate ruxolitinib versus best available therapy for patients with SR-GvHD as second line of therapy.