Closing Thoughts on the GVHD Treatment Landscape

EP: 1.Patient Profile: A 35-Year-Old Woman with Chronic GVHD

EP: 2.Allogeneic Transplantation and GVHD Prophylaxis

EP: 3.Overview of Acute and Chronic GVHD

EP: 4.Treatment Considerations for Chronic GVHD

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EP: 5.Closing Thoughts on the GVHD Treatment Landscape

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%)

Transcript:

Nelson J. Chao, MD: This is a patient now a year out of transplant with a score of 2 muscle and joint pains limiting her daily exercise routine. I would have treated her with prednisone as well. I would have started at 1 mg/kg per day to see how she responded. If she responded well, I would have slowly tapered down over the course of several months to be off prednisone. If she did not respond and she still had this score of 2 muscle problems, I would have added ruxolitinib at this point.

As we tried to taper down the steroid, [this patient] developed a score of 2 mouth symptoms with ulceration with lichenoid features. A score of 2 in the mouth suggests that she was having some difficulty eating. At that point, with a steroid taper, I would have gone back up to about 0.5 mg/kg and then added ruxolitinib to her regimen. And I would have expected her to respond. If she did not respond after 4 to 8 weeks, I would have added belumosudil to this patient.

Advances in the GVHD [graft-vs-host disease] space is one of the more interesting aspects. Remember, the best prevention of chronic GVHD is preventing acute [GVHD]. Acute GVHD prevention strategies include using post-transplant cyclophosphamide, which has decreased incidence of acute GVHD and therefore also chronic GVHD. Other strategies are 2 randomized phase 3 trials using alpha-1 antitrypsin as prophylaxis. Those studies have accrued, and we’re waiting for the data to mature.

Other things include abatacept, which has been approved in mismatched donors, decreasing acute GVHD. They’re studied with histone deacetylase inhibitors, preventing acute GVHD. There are cell therapies using, for example, regulatory T cells to try to decrease acute GVHD. Each time you can decrease acute GVHD, as a correlation, you should be able to decrease chronic GVHD as well.

Biomarkers are useful. We are still waiting for prospective randomized phase 3 trials [to confirm] the full validity of these. I think there’s enough data to suggest that using the biomarkers that exist today allows us to have a better sense of which patients will do better even though they’ve been diagnosed with acute GVHD, compared with those patients who are going to do very poorly and probably require more therapy rather than less.

Transcript edited for clarity.