Therapy Options for Patients with Chronic GVHD

EP: 1.Patient Profile: A 48-Year-Old Man with Chronic GVHD

EP: 2.Transplant Conditioning Regimens and GVHD Prophylaxis

EP: 3.Overview of GVHD Types and Symptoms

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EP: 4.Therapy Options for Patients with Chronic GVHD

EP: 5.Treatments for Steroid-Refractory Chronic GVHD

EP: 6.Second-Line Approaches to Treating GVHD

EP: 7.Clinical Insights on the Future of GVHD Treatment

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

Transcript:

Yi-Bin Chen, MD: Starting systemic therapy for chronic graft-vs-host disease [GVHD] can be a difficult decision at times. It depends on what organs are involved. As I said before, the eyes, the mouth, and the skin are the most common organs. In all honesty, manifestations of the eyes and the mouth are probably best treated locally. In our management algorithm, or our management style, we consult and collaborate extensively with our colleagues in ophthalmology and oral medicine to help our patients develop improvement in their ocular and oral manifestations. For skin manifestations, we also work with our dermatologists, and for those that involve limited body surface areas, I think we would try to focus on topical therapies.

Once the body surface area grows or is in a place the patient can’t reach to apply those topical medications, or shows evidence of scleroderma, it would be time to consider systemic therapy. Multiorgan involvement probably should trigger a discussion of systemic therapy. If someone has ocular, oral, and skin manifestations, while you can give localized therapy to all those organs, you have to acknowledge that it’s become a systemic disease at that point, and would probably be best treated with local and systemic therapies.

In general, for patients with mild chronic graft-vs-host disease, overall, we try to stick with localized therapies. Then once they move to moderate to severe, we start to think about it and work in, is it multiorgan, how severe it is, and what organs are involved. Using steroids or adding steroids to someone’s regime at this point is not a trivial decision. Many patients, such as this patient, have had acute graft-vs-host disease in the past and have already had a long course of systemic steroids. Many of them have experienced the morbidities of being on that long course of steroids. They have proximal muscle wasting, they are quite weak, their body habitus has changed. We may have caused type 2 diabetes; we may have caused more hypertension. Their bone density is undoubtedly less. They’re certainly more at risk for opportunistic infections because of the use of long-term steroids. So adding them back, restarting them, or even increasing them if they’re still on a small dose is not a trivial decision and adds to their morbidity at that point. But at this point, systemic steroids remain the standard first-line therapy if one is using systemic therapy for chronic graft-vs-host disease.

In terms of dosing, the consensus would say anywhere from 0.5 to 1.0 mg/kg per day of prednisone equivalent to start. In our practice, we generally start around 0.5 mg/kg per day and see how it goes over the next 4 weeks. We tend to try to keep that dose the same for at least 4 weeks to figure out if their manifestations or their disease are steroid responsive. None of us in the community are satisfied with steroids as first-line therapy, but that remains the standard. There are a number of patients who benefit from steroids. In my experience, probably two-thirds of patients I start on steroids for chronic graft-vs-host disease will, at some point in their course, require a second-line agent, whether for refractory disease, or a partial response that’s not satisfactory, or because we need to spare steroids because of comorbidities, so we add something else. Or maybe the patient responded but as we taper steroids, they have a recurrence or a flare of symptoms and are less steroid dependent, and we need to add a second-line agent to get rid of those steroids. But it isn’t great; it is not a great therapy. I think one of the huge priorities in our field is to move beyond steroids for first-line treatment.

Transcript edited for clarity.