Second-Line Approaches to Treating GVHD


Yi-Bin-Chen, MD, discusses the effect of GVHD recurrence and multiple-organ involvement on treatment decisions.

Case: A 48-Year-Old Man with Chronic GVHD

  • 48-year-old man undergoes myeloablative conditioning followed by matched unrelated donor hematopoietic cell transplant for acute myeloid leukemia w/ tacrolimus + methotrexate as graft versus host disease prophylaxis
    • The donor is a cytomegalovirus seropositive 50-year-old woman with 3 children
  • Day +22, acute GvHD of skin emerged, successfully treated with slow steroid taper
  • Bone marrow testing performed at 6 months and 12 months post-transplant show AML in complete remission
  • 1.5 years post-transplant, new-onset skin changes with hyperpigmentation, lichen-planus and superficial sclerodermatous-like features on lower trunk and lower extremities (not confirmed); 15% BSA involved
  • Prednisone initiated, initial dose 0.5 mg/kg/d (max 10 mg/kg per week), then 4-week taper
  • After 7 days of prednisone, initial improvement in BSA involvement (now 10% to 15%), with no improvement in range of motion, remained stable thereafter on 0.5 mg/kg every other day


Yi-Bin Chen, MD: If we look at our patient, they had a partial response and are stable on 0.5 mg/kg every other day of prednisone. Based on that information, it’s hard to summarize into words what we would do. Our job and goal is to sit down with the patient and family and have a long discussion of our expectations and what our options are. In the past, when we didn’t have great options, and our options involved cumulative immunosuppression, I would have been loath to think about adding another treatment. Photopheresis might have been a reasonable thought, given it doesn’t add cumulative immunosuppression, and rituximab might have been OK as well.

But these days, I’d discuss the novel agents that we have. I’d assess the patient’s satisfaction with their quality of life and what their goals are. I’d also look at the patient and his/her comorbidities to figure out what the steroid dose would do in the long run. For this patient, I’d recommend starting ruxolitinib for 2 reasons: to augment the partial response—to improve the partial response that he has achieved with steroids—but more important to reduce the dose of steroids and maintain that response. That’s what I’d do, but our job is to decide with the patient, explaining what we know and what we don’t know. I’d start there. Ruxolitinib has been our standard second-line therapy for chronic graft-vs-host disease for several years. We’ve had very good success with it. It appears to be a very safe agent, except for a subset of patients who might experience cytopenia that requires monitoring.

It’s attractive to think about belumosudil at this point. Even though the therapy was studied in the third-line setting, we all know it’s safe in the second-line setting. Because the patient’s primary manifestation is scleroderma and the mechanism of action is belumosudil, it would be a consideration. Those 2 would be my top candidates for sequencing going forward.

It’s always important to remember that we should try to do clinical trials to improve therapy. If there were an attractive clinical trial open at our institution, that would be a strong consideration. If the patient had more than limited scleroderma of the skin, we probably wouldn’t push, but we’d probably recommend second-line therapy earlier and in a stronger fashion, given the systemic nature of the illness and the desire to prevent progression or spread to other organs. Those are the conversations we’d have with the patient and the thought process about how to treat this disease.

Transcript edited for clarity.

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Yi-Bin Chen, MD, an expert on GVHD
Yi-Bin Chen, MD, an expert on GVHD
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