Treatment Options for Chronic GvHD


Corey S. Cutler, MD, MPH, FRCPC: What are the treatment options for this patient? This case is de novo chronic graft-versus-host disease [GvHD], and the standard of care is to treat with corticosteroids. Steroids are generally given at a dose of 0.5 to 1 mg/kg of body weight, usually 0.5 mg/kg per day or 1 mg/kg every other day. However, some clinicians will start at a dose of 1 mg/kg per day. In general, doses higher than that are not recommended in chronic graft-versus-host disease. There is some evidence that adding a calcineurin inhibitor at the onset of chronic GvHD might decrease steroid burden over time, although it does not increase response rates. Some of us clinicians will add drugs like tacrolimus or cyclosporine at the time of initial therapy for chronic graft-versus-host disease.

For chronic GvHD, most of us will treat at a minimum for 4 weeks at a single steroid dose, and up to 3 months has been often the classic teaching in this disease. We generally wouldn’t consider someone steroid-refractory unless they were progressing after several weeks of therapy or really had no response after a good trial of 2 to 3 months of therapy. There are certain clinical scenarios, particularly those that are involving scleroderma or progressive lung disease that merit earlier switch to a second-line agent.

In terms of the drugs that we use for the second-line setting, there’s only 1 drug that is approved at this point and that is ibrutinib. Ibrutinib is approved based on a 42-patient study done, an open-label phase 2 trial that demonstrated a response rate of about two-thirds in patients with steroid-refractory chronic graft-versus-host disease. So ibrutinib is the de facto second-line agent. We also recommend participation in clinical trials whenever possible, and there are a number of exciting compounds that are being tested these days for second-line therapy and beyond for chronic graft-versus-host disease.

Transcript edited for clarity.

Case: A 49-Year-Old Man With Steroid-Refractory Chronic Graft Versus Host Disease

Initial presentation

  • A 49-year-old man complains of “color and texture” changes to his skin, nails and the inside of his mouth; he also complains of shoulder and elbow joint discomfort limiting his normal daily activity
  • PMH: he underwent matched related allogenic transplant from his brother for treatment of AML
  • PE: depigmentation and lichen planus-like features noted on his chin, nose, cheeks and forearms bilaterally, and in the oral mucosa (~40% BSA); longitudinal ridging of the fingernails; joint stiffness and decreased range of motion

Clinical workup

  • Labs: plt 70 x 109/L, total bilirubin 7.6 mg/dl, AST 150 U/L, ALT 165 U/L, ALP 430 U/L
    • Negative for HBV, HBV, CMV, EBV, HHV-6
  • NIH Global Severity of cGvHD moderate cGvHD; P-ROM score 4
  • ECOG 1


  • Tacrolimus + dexamethasone oral rinse
    • No treatment response after 4 weeks
  • He was started on ruxolitinib 5 mg PO BID which was tolerated well; increased to 10 mg PO BID on day 6
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