Emerging Agents for the Treatment of Chronic GvHD


Corey S. Cutler, MD, MPH, FRCPC: There are a lot of other drugs being tested in graft-versus-host disease and a lot of other approaches. We’re targeting multiple cytokines and multiple pathways. People are very interested in both the B-cell and T-cell side of things, as well as directly inhibiting cytokines. There remains some interest in the use of extracorporeal phototherapy.

One of the more promising drugs that’s being developed is the ROCK2 inhibitor KD025. This drug has been tested in an open-label phase 2 dose escalation study and then more recently in a randomized phase 2 trial where 2 different doses were tested. In this study, which was presented at the last meeting of the Transplantation & Cellular Therapy Meetings, the drug was noted to have a response rate of approximately 65%. This was in patients who were heavily pretreated, between 2 and 5 lines of prior therapy. It turned out that individuals who had received prior ibrutinib or ruxolitinib had very good responses, and individuals with both moderate and severe graft-versus-host disease responded very nicely to it. We wait to see the long-term results of that study. The results I just presented were the results of an interim planned analysis, and the final analysis will occur after all patients have been followed for 12 months on the study.

There are other compounds that are being tested along the lines of the ROCK inhibitors, and we’re anxiously waiting for those compounds to complete their clinical trials because quite frankly, chronic graft-versus-host disease still is suboptimally treated, and we don’t have enough tools in the tool kit to treat it today.

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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