How I Treat a Patient With Triple-Relapsed Chronic Graft-Versus-Host Disease
Shernan Holtan, MD, Roswell Park Comprehensive Cancer Center, Buffalo, New York, outlines a treatment plan for a patient with triple-relapsed chronic graft-versus-host disease (GVHD).
Dr Holtan explains and provides evidence for the next line of treatment a clinician may consider in this particular situation.
Transcript:
I'm Shernan Holtan and I'm the chief of blood marrow transplant at Roswell Park Comprehensive Cancer Center, discussing a case of chronic graft-versus-host disease today.
I have a 52-year-old man who underwent peripheral blood stem cell transplantation from an HLA-matched sibling donor for high-risk myelodysplastic syndrome (MDS). Conditioning was with fludarabine and melphalan, and graft-versus-host disease prophylaxis was with tacrolimus and methotrexate. By 9 months post-transplant, the patient developed multi-organ chronic graft-versus-host disease. This involved his skin with an erythematous rash that eventually progressed to some sclerosis, oral mucosa, which included painful ulcers and sensitivity in his mouth, ocular involvement, which included dry eyes, pain and sensitivity, as well as the GI tract, which resulted in diarrhea and abdominal cramping.
He was initially treated at this presentation with first line sirolimus and prednisone. This provided some partial improvement, but sirolimus was ultimately discontinued due to concerns of peripheral edema, as well as cytopenias. Subsequently, ibrutinib was initiated for the persistent rash and mucosal disease. This also led to some clinical improvement, but the patient had worsening diarrhea that got to be so significant that he had to stop the drug.
Subsequently, when the disease flared again, he was started with ruxolitinib. This also provided moderate control of his symptoms, but he developed multiple infections throughout his treatment. This included bacterial respiratory infections as well as herpes virus reactivation.
The patient was then started on belumosudil as something that may be a little bit less immunosuppressive, but he developed worsening sclerosis of his skin. The sclerosis progressed to the point where he had disabling skin thickening, joint stiffness, and impaired mobility.
Given the refractory nature of his chronic graft-versus-host disease, the next step in his management for us was axatilimab. We have a question to consider here, and that question is, which of the following considerations most appropriately supports the decision to initiate axatilimab in his patient? A: the history of intolerance to ruxolitinib due to infectious complications; B: the presence of refractory multi-organ chronic graft-versus-host disease with progressive skin sclerosis that was unresponsive to multiple prior lines of therapy. C: the potential for axatilimab to reverse oral mucosal ulcerations; or D: the lack of response to tacrolimus and methotrexate prophylaxis, indicating a poor prognosis. The best choice here is the presence of refractory multi-organ chronic graft versus host disease, with in particular, progression to skin sclerosis that was unresponsive to multiple prior lines of therapy.
Axatilimab is the newest FDA-approved drug for chronic graft-versus-host disease, and is unique. This is a monoclonal antibody that is targeting [colony-stimulating factor 1 receptor] (CSF1R). This is targeting those pro-fibrotic macrophages in chronic graft-versus-host disease. This may be a particular benefit in those with fibrotic features, especially where prior lines of therapy have failed to improve symptoms. In this case, that was the natural next selection for therapy for this patient.
Thank you for considering this patient case, and we'll continue the discussion online.
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