Translating Innovation Into Practice: Emerging Treatments and Real-World Data in GVHD - Episode 6
Case 2: cGVHD With Ocular and Hepatic Involvement
Panelists discuss how a 48-year-old female patient with chronic GVHD involving ocular, hepatic, and skin manifestations presents diagnostic challenges when elevated liver enzymes could indicate disease progression or drug toxicity from belumosudil and axicabtagene ciloleucel, leading to consideration of alternative treatments like mycophenolate or the preference for axicabtagene ciloleucel in patients with prior treatment failures or significant lung involvement despite the lack of head-to-head comparative data.
Case 2: cGVHD With Ocular and Hepatic Involvement
This segment presents a 48-year-old woman who underwent myeloablative allogeneic transplant for acute lymphoblastic leukemia with posttransplant cyclophosphamide, tacrolimus, and mycophenolate prophylaxis. Ten months post transplant, she developed chronic graft-vs-host disease (GVHD) with diffuse lichenoid rash, progressive skin tightening, severe dry eyes with corneal damage, painful oral ulcerations, and moderate asymptomatic elevation of liver enzymes (AST/ALT). Unlike the first case, she had no pulmonary involvement. Initial treatment with prednisone 1 mg/kg daily for 2 weeks showed marginal improvement, meeting criteria for steroid-refractory disease. Second-line ruxolitinib 10 mg twice daily provided modest liver improvement at 4 weeks but persistent skin, ocular, and oral symptoms.
The discussion addresses the diagnostic challenge of elevated liver enzymes in transplant patients, who frequently have multiple potential etiologies including medications, infections, and GVHD. Liver biopsy is rarely performed due to invasive nature and associated risks. Initial steroid response serves as a diagnostic indicator for GVHD-related hepatic involvement. Additional supportive markers include elevated alkaline phosphatase and total bilirubin creating a constellation suggestive of hepatic GVHD. Imaging studies (ultrasound, MRI) help exclude other causes like fatty liver or biliary obstruction. For predominant liver involvement, alternative therapies include mycophenolate mofetil, rituximab, sirolimus, or extracorporeal photopheresis before considering novel agents.
Treatment selection between belumosudil and axatilimab becomes complex when hepatic involvement is present, as both agents can cause liver enzyme elevation through different mechanisms: axatilimab through CSF-1R targeting of Kupffer cells and belumosudil through direct hepatotoxicity requiring monthly monitoring. Most clinicians prefer belumosudil first due to oral administration convenience and greater clinical experience. However, axatilimab may be preferred in patients who have failed multiple prior therapies, given the AGAVE-201 trial data showing responses even in heavily pretreated patients, and particularly for those with pulmonary involvement where response rates appeared higher. The paradoxical finding that patients with more prior treatment lines responded better to axatilimab supports its use in refractory cases, though direct comparative efficacy data between these agents remains unavailable.
Related Content:
