Using Ruxolitinib to Treat Steroid-Refractory Acute GVHD


The rationale for treating steroid-refractory acute graft-versus-host disease with ruxolitinib, a JAK inhibitor, and recommendations for monitoring and managing treatment-related adverse events.

Michael Bishop, MD: Ruxolitinib is an interesting molecule. We know that the JAK pathway plays an important role in numbers of cells, but it also plays an important role in T cells. T cells mediate graft-versus-host disease. And so, it can lead to T-cell activation, important cytokine production, trafficking of T cells. Based on this knowledge, people had the clever idea of, “If it does all those things and T cells are mediating graft-versus-host disease, maybe we can use ruxolitinib as treatment for graft-versus-host disease.

This was first tested this in murine models, and the drug was very good at treating mice with established graft-versus-host disease. Now, that doesn’t always translate well into humans. However, there were some early studies where people did use ruxolitinib, because it’s approved for other indications, and we saw some initial preliminary responses. And then there was the REACH1 study, which demonstrated that patients with steroid-refractory disease had responses to this therapy. That’s what led to the development of the phase 3 REACH2 study.

The major adverse event that we think about with ruxolitinib is myelosuppression. It’s very important to monitor platelets and neutrophil counts during therapy. That correlates with infection, and there can be neutropenic fever. In the trial, there was an increased risk of respiratory infections. Again, if you think you’re inhibiting T cells, you have to worry about an increased risk of viral infections. There was a higher incidence of viral infections. There was an overall higher risk of infections in general, but particularly pulmonary and upper respiratory infections. There can be some mild elevations in liver enzymes and creatinine, but those are easily manageable on a relative scale. It’s really those blood counts and infections that we worry about the most.

Transcript edited for clarity.

Case: A 53-Year-Old Man With Steroid-Refractory Acute Graft-Versus-Host Disease

Initial presentation

  • A 53-year-old man presents on day +40 for a routine follow-up visit after matched donor peripheral blood stem cell transplant. He complains of a new rash, abdominal pain and ‘countless’ loose stools every day for the last 4 days
  • PMH: unremarkable
  • PE: Rash noted on arms and upper trunk (~45% BSA); diarrhea was quantified to about 1100 cc/day

Clinical workup

  • Labs: total bilirubin 2.6 mg/dl, AST 60 U/L, ALT 75 U/L, Hb 9.8 g/dl
  • Negative for HBV, HBV, CMV, EBV, HHV-6
  • Stool testing negative for bacterial/viral infection
  • Skin biopsy of the rash showed exocytosed lymphocytes, and dyskeratotic epidermal keratinocytes with follicular involvement
  • Colonoscopy with biopsy showed numerous apoptotic bodies in the crypt epithelium
  • He was diagnosed with acute GVHD:
    • Skin stage 2
    • GI stage 2
    • Liver stage 1
    • Modified Glucksberg Criteria: grade II; MAGIC Criteria: grade II
  • ECOG 1


  • Initiated methylprednisolone 1.0 mg/kg and topical steroids
  • There was minimal response to treatment after 2 days, dose was increased to 2.0 mg/kg/day
  • Continued on systemic steroids for 5 more days; rash subsided minimally
  • He was started on ruxolitinib 5 mg PO BID, tolerated well; increased to 10 mg PO BID at day 3

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