Future Directions and Unmet Needs in Chronic GvHD

Corey S. Cutler, MD, MPH, FRCPC: In terms of future directions and unmet needs in chronic graft-versus-host disease [GvHD], unfortunately there are several. First, we need to find better ways of preventing the disease. Probably the most promising way of preventing chronic graft-versus-host disease is using an approach around the time of transplant that will prevent it entirely. For example, the use of post-transplantation cyclophosphamide has been associated with lower rates of chronic graft-versus-host disease, and there are some interesting and novel strategies around T-cell manipulation or T-cell depletion that might also be very promising for preventing chronic graft-versus-host disease. There are some clinical trials testing interventions using B-cell–depleting approaches or B-cell therapeutics to try to prevent graft-versus-host disease, but we have not yet seen the readout of those trials.

I think another factor in chronic GvHD that’s often overlooked is the supportive care of the individual organs. For that, I would point the viewers toward a comprehensive set of guidelines from the American Society for Transplantation and Cellular Therapy [ASTCT]. We have an NIH [National Institutes of Health] consensus document that is published on the ASTCT website. The most recent version is from 2014 and discusses all the supportive care measures that can be delivered to each individual organ, both topically and systemic supportive care for individual organs.

Finally, there are issues related to the long-term use of corticosteroids and prevention of corticosteroid-related toxicity. These include preventing osteoporosis, managing glucose intolerance, hypertension, managing weight and weight changes associated with chronic steroid use, and the psychological support of being on chronic corticosteroids. All of these are really important things that one has to consider when starting corticosteroids for chronic graft-versus-host disease and especially in the general care of the chronic GvHD patient.

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
  
  

Treatment

• 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