Managing Chronic GVHD for a Patient After Progression

Chronic graft-vs-host disease (GVHD) is a cause of late morbidity and mortality after allogeneic stem cell transplant. During a virtual Case-Based Roundtable, Hannah Choe, MD, an associate professor of Internal Medicine in the Division of Hematology at The Ohio State University, detailed the case of a steroid-dependent chronic GVHD. Choe and the event participants explored the critical decision of whether to increase steroid dosage or to add a second-line agent.

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CASE SUMMARY

• A 48-year-old man underwent a myeloablative conditional matched unrelated donor hematopoietic cell transplant for acute myeloid leukemia (AML) with tacrolimus plus methotrexate as graft-vs-host disease (GVHD) prophylaxis.
• The donor was a 50-year-old woman with 3 children who is seropositive for cytomegalovirus.
• After day 22, acute GVHD of the skin emerged and was successfully treated with slow steroid taper.
• Results from bone marrow biopsy performed at 3 months post transplant showed AML in complete remission.
• He returned at 6 months post transplant with normal blood counts. He presented with skin changes with hyperpigmentation, with approximately half of each arm showing lichen planus; superficial sclerotic features (able to pinch the skin) on the lower trunk and lower extremities; 18% body surface area (BSA) involved; and no decrease in forced expiratory volume in first second of expiration/diffusing capacity of the lung for carbon monoxide on pulmonary function test results.

DISCUSSION QUESTIONS

• How would you approach the treatment plan for this patient with GVHD?
• How long should this patient be treated with first-line therapy?
• What other adjunctive/supportive therapies do you implement at initial presentation?

Hannah Choe, MD: If you were to plug this all into the National Institutes of Health scoring system, you would use the higher of the features and the score for skin, and that would give you stage 2. This patient automatically has at least moderate skin GVHD.

How would you approach the treatment plan for this patient? How long should you treat this patient with first-line therapy? And what else would you do when you first see the patient to try and make sure that you're managing the patient as best you can?

Bramham Reddy, MD: We don't have that much experience [with this] in a small town. I would be in touch with the transplant center. We do have good contact directly, and most of these patients know whatever they recommend, [we should go with].

Choe: Does anybody have a specific approach they take?

Andrew P. Dalovisio, MD: I’d probably restart steroids and possibly tacrolimus for acute control and then start talking about starting another agent like ruxolitinib [Jakafi].

Tejo N. Musunuru, MD: It's about 18% involvement, which is mild to moderate, so I probably start with the steroids first, and assess for a response before going on to further lines of therapy. But we have, I would say, probably something that we didn't have 10 years ago is a lot more treatments these days.

CASE UPDATE

• Prednisone was initiated with an initial dose 1 mg/kg per day.
• After 7 days of prednisone, initial improvement in BSA involvement
• Patient received taper, however, increased in BSA involvement from 15% to 20% during prednisone taper.
• A subsequent taper was attempted unsuccessfully.
• Symptoms remained stable thereafter on 0.25 mg/kg per day for 1 month.

Choe: Some would maintain the same steroid dose. Some would watch and if the disease progresses, increase the steroid dose, and some would change therapy. Between managing the steroids vs moving on to another therapy, I have to say that it does depend on how the patient is responding and how quickly…. I change to new therapies given the toxicity of steroids and the lack of anticipated improvement on the same steroid dose, or even increasing steroid dose, particularly if [they are on a high dose of steroids]. Even with 0.25 mg/kg, it's the kick that I'm anticipating. We're not going to be able to wean unless we start another line of therapy.

Bipin Amin, MD: When you talk about changing therapy, are you saying stop the steroid and go to something else, or you add in addition to steroids?

Choe: You can add in addition to steroids, but then what I do personally depends on the tolerance of steroids. I will add therapy and taper at the same time. I'll stagger it by about a week, but essentially, at the same time.

Dalovisio: Do you generally restart a calcineurin inhibitor, like they were on previously?

Choe: It depends on the timing; it depends on how long ago that calcineurin inhibitor or mTOR inhibitor was weaned off. If it was very recent, it was very clearly during that tapering. I will go back on if it is a mild progression, but if it's significant progression, then I don't bother because I don't anticipate that adding calcineurin inhibitor back on will be helpful, knowing that I'm only going to be adding on a larger and more effective immunosuppression with another therapy.

Musunuru: It looks like this patient was only on the steroids for 1 week with some initial improvement and the milder erythema. What is your timeline to add or switch to a new therapy? Is that too soon?

Choe: There are definitions of steroid-resistant vs steroid-dependent chronic GVHD. When a patient has progressed after 7 days of steroids, they're at least steroid dependent, if not steroid resistant. Then if they're requiring at least 0.25 mg/kg per day over 1 to 2 months, then they are steroid dependent. In this case, this patient was steroid dependent/steroid resistant. We do have a history that they were weaned off, after 1 week they progress, and then they did improve, but then had progression on low-dose steroids.

Typically, for a patient, we'll give them around 4 weeks or so to assess. If they're progressing rapidly though, I don't waste any time. If the patient has progression—for example, having difficulty eating, that's happening within a week—I'm not going to let them sit on steroids and wait for the steroids to work. It is always case based, but I also do not hesitate to try to get off steroids earlier in general.

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_{DISCLOSURES: Choe previously reported relationships with Incyte Corporation, Sanofi, Ironwood Pharmaceuticals, AbbVie, Actinium Pharmaceuticals, Inc., and Regimmune.}