The Future of GVHD Management

Usama Gergis, MD: Just to summarize, graft-versus-host disease [GVHD] is 1 of the most common adverse events after allogeneic transplant. The acute disease state takes place earlier, the first 100 days or so, after transplant. Chronic disease takes place later. Acute disease is acute inflammatory T-cell driven. Chronic is more of an autoimmune fibrotic phenomena. Acute disease affects approximately 40% to 80% of patients. Chronic disease affects approximately 40% to 50% to 60% of patients. Many variables affect the incidence of acute graft-versus-host disease, such as the severity and other prognostic indicators.

The treatment for both—the first-line treatment is usually corticosteroids. For patients with acute graft-versus-host disease, most of the time, the initial dose is 2 mg/kg prednisone or the equivalent. It’s easy to know earlier whether patients will respond—50% generally will respond, 58% will not respond or respond but become dependent on the steroids. The second-line treatment and the only FDA-approved second-line treatment for steroid-refractory acute graft-versus-host disease is ruxolitinib. And, again, the response rate is approximately 50%.

You can tell from my summary I’m semi-optimistic. In the past 50 years or so since the inception of allografting, there was nothing better to add to glucocorticosteroids. Now that we have ruxolitinib as an approved agent that was confirmed in a state-of-the-art phase 3 trial, there is a lot of excitement for our community but we want more. We still have 50% of patients who will not respond. We still have people who respond initially and then they fully erupt and they lose that response. Even for the responders, the intense immune suppression leads to increased mortality—50% treatment-related mortality at 6 months, 60% treatment-related mortality at 1 year. So, the picture is not so good. I am shy of saying dismal. We have nothing better than steroids at this point to treat chronic graft-versus-host disease. But there are a lot of other agents in the pipelines. We are running a multitude of trials in various treatment modalities, so I am optimistic that soon enough we will have a couple of other agents for these 2 very difficult-to-treat diseases.

Transcript edited for clarity.

Case Overview:

Initial presentation

• A 61-year old man presented with a generalized pruritic rash, abdominal pain and diarrhea (8-12 BMs/day)
• PMH: he underwent haploidentical allogeneic hematopoietic-cell transplantation for AML 40 days ago
• PE: maculopapular erythematous rash on bilateral palms, cheeks, ears and upper back (rash involvement >50% of skin); abdomen is tender to palpation diffusely
  
  

Clinical workup

• Labs: ANC 0.7 x 109/L, plt 75 x 109/L, total bilirubin 8 mg/dl, AST 54 U/L, ALT 60 U/L
  • Negative for HBV, HBV, CMV, EBV, HHV-6
• Negative stool tests
• Flexible sigmoidoscopy with biopsy:
  • Lower GI biopsy showed moderate mixed inflammation in the lamina propria and scattered apoptotic bodies without crypt loss
• Skin punch biopsy of the back shows hyperkeratosis, hypergranulosis associated with lichenoid inflammatory infiltrate
• Modified Glucksberg criteria: grade 3; MAGIC criteria: grade III
  
  

Treatment

• Systemic corticosteroids (prednisone 2 mg/kg/day) + topical steroids (triamcinolone)
  • No treatment response after day 5
• He was started on ruxolitinib 5 mg PO BID, increased to 10 mg PO BID on day 6