Treatment Considerations for Chronic GVHD


A GVHD expert outlines the treatments available for patients with chronic GVHD and steroid-refractory chronic GVHD.

Case: A 35-Year-Old Woman with Chronic GVHD

  • A 35-year-old woman received busulfan and cyclophosphamide conditioning prior to a matched unrelated donor peripheral blood stem cell transplant for acute myeloid leukemia; tacrolimus and methotrexate were administered as graft-vs-host disease prophylaxis.
  • PMH of type 2 diabetes.
  • Post-transplant, experienced the following:
    • +1 month post-transplant, grade II acute skin GVHD, resolved with glucocorticoids
    • +6 months post-transplant, grade I vaginal dryness, treated with topical estrogen
    • +11 months post-transplant, grade I dry eyes/foreign body sensation, treated with lubricating eye drops
  • Now, + 12 months post-transplant, grade 2 muscle and joint paint that limits daily exercise routine, treated with prednisone
  • Supportive care and counseling provided
  • 1 mg/kg/day prednisone tapered to 0.25 mg/kg/day
  • During steroid taper, patient developed grade 2 mouth symptoms with ulceration and lichenoid features as well as maculopapular rash/erythema on lower torso (BSA 10%)


Nelson J. Chao, MD: The treatment options of chronic GVHD [graft-vs-host disease] are increasing, which is a good thing. The most important thing is to treat early, and the reason is because in chronic GVHD, there’s a sclerosis that goes on. If a patient is treated very late in the process of their disease, it becomes much more difficult to reverse the fixed sclerotic changes. One of the problems with chronic GVHD is that the patient is no longer at the transplant site. They’re usually home, they’re not being followed as frequently, and if they start having symptoms, they may not be aware or may not pick up [on them]. The organ where this is most problematic is the lung, where patients start to develop pulmonary bronchiolitis obliterans. If that isn’t picked up early, they’ll end up with severe defects and potentially die of lung GVHD.

What will we do? If the patient has just tapered off their cyclosporine and they flare within 4 to 8 weeks, I restart the immunosuppressive drugs that they were on. Otherwise, I use steroids up front—usually at 0.5 to 1 mg/kg, depending on the extent of their disease and how quickly their disease is progressing. I use this for several weeks to see if they’re responding. If they have a response, I try to taper them down over 2 to 3 months. Because this is chronic [GVHD], you have a little time. But within 2 to 4 weeks, if they’re not getting better, I’d add a second drug. If they’re clearly getting worse after a couple of weeks, I’d add a second drug then as well. There are patients who have psychosis with steroids or patients who have diabetes, like this patient—once you put them on steroids, their diabetes becomes very difficult to control. We try to taper the steroids as much as we can and add another agent.

For steroid-refractory or steroid-intolerant chronic GVHD, we have 3 drugs available. The first drug approved by the FDA was ibrutinib. That was approved with a very small study, about 49 patients, where they did see about a 65% to 70% response rate. Ibrutinib isn’t used very frequently, primarily because it’s a very difficult drug to use in these patients. Adverse effects of ibrutinib are cytopenias and diarrhea, and many of these patients start with cytopenias and diarrhea. It’s a more difficult drug to use. It was also approved on a very small phase 2 trial.

Ruxolitinib was approved on a prospective randomized phase 3 trial with 349 patients randomized to ruxolitinib vs best supportive care or best alternative therapy. That study was significantly positive for ruxolitinib, where 65% to 70% of the patients had an overall response and improved. That response was sustained for several years, suggesting that there’s the potential of controlling this disease.

Both ruxolitinib and ibrutinib are approved in the second-line setting after steroids. Belumosudil was approved in the third line after the failure of 1 of those drugs. Belumosudil was also approved based on a phase 2 study, and those data were very encouraging. The most encouraging thing about belumosudil was that the response rates were high, similar to ruxolitinib and ibrutinib. But 2 things stood out. One was that the toxicity profile was quite benign. Patients seemed to tolerate this quite well. Also, there was a clear response in patients with chronic GVHD, which has historically been a very difficult patient population to treat.

Another drug that has commonly been used off-label has been extracorporeal photopheresis [ECP]. ECP is used in many centers that have ECP as a way of controlling chronic graft-vs-host disease, usually after failure of ruxolitinib. The downside of ECP is that they need a central line, and they have to come to the center at least twice a week when they start for the therapy. But that’s also used frequently in centers that have it. Other drugs that have been tried include abatacept, alemtuzumab, hydroxychloroquine, low-dose IL-2, rituximab, and pentostatin. Those all have response rates of 20% to 25%, and specific subsets of patients may respond to these drugs a little better than others. But there are no phase 3 randomized trial data for these other drugs.

Transcript edited for clarity.

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