Treatment Sequencing and Organ-Based Considerations in Chronic GVHD

Treatment Sequencing and Organ-Based Considerations in Chronic GVHD

This segment addresses treatment selection strategies for patients with multiorgan chronic graft-vs-host disease (GVHD), particularly those with concurrent skin and pulmonary involvement who have failed second-line therapy. The specialists acknowledge that clinical trials were designed to assess overall response rates rather than organ-specific efficacy, making treatment selection challenging. For patients previously exposed to ruxolitinib, the 2 remaining FDA-approved options are belumosudil and axatilimab. The AGAVE-201 trial data suggests potential advantages for axatilimab in pulmonary GVHD, with nearly 100% of 260 enrolled patients having lung involvement and approximately 47% achieving organ response and FEV1 stabilization compared to 30% with other agents, though these represent raw data comparisons rather than head-to-head trial results.

Practical considerations significantly influence treatment selection beyond efficacy data. Axatilimab requires biweekly intravenous infusions, necessitating patients to travel to treatment centers since home infusions are not currently available. This creates challenges for patients living far from transplant centers who may prefer oral agents like belumosudil. Patient willingness to maintain vascular access, undergo frequent laboratory monitoring, and spend time for infusions must be weighed against potential therapeutic benefits. The decision-making process involves interpreting available trial data, considering individual patient factors, physician experience, and practical logistics rather than definitive comparative efficacy data.

Axatilimab presents unique monitoring considerations due to its mechanism targeting CSF-1R and macrophage populations, including hepatic Kupffer cells responsible for enzyme clearance. This results in predictable elevations of liver enzymes (AST, ALT), muscle enzymes (LDH, CPK), and pancreatic enzymes (amylase, lipase) that typically remain below serious toxicity thresholds. The discussion concludes with future therapeutic aspirations, emphasizing the need for predictive biomarkers to guide treatment selection. Research is developing blood-based biomarkers measurable at day 100 post transplant that could predict GVHD development and guide pathway-specific interventions. The ultimate goal involves preemptive treatment strategies based on elevated biomarkers like TNF-α, MMP-9, or interferon signatures, potentially preventing symptom development entirely through early targeted therapy.