Clinical Perspectives for Sequencing Therapies in SR cGvHD

EP: 1.An Overview to cGvHD

EP: 2.A Review of Approved Therapies for SR cGvHD

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EP: 3.Clinical Perspectives for Sequencing Therapies in SR cGvHD

EP: 4.Real-World Experience with Ruxolitinib in SR cGvHD

EP: 5.Emerging Treatment Practices in cGvHD Care

Ruxolitinib and Axatilimab for Chronic GVHD Treatment

Ruxolitinib, the third approved drug for chronic GVHD, was evaluated in the REACH 3 study, a multicenter phase 3 clinical trial enrolling approximately 300 patients. The primary endpoint of six-month overall response rate showed significant improvement with ruxolitinib 10mg twice daily compared to best available therapy (50% vs. 25%). Patients on ruxolitinib also demonstrated improved failure-free survival, though the main side effects included cytopenias and infections requiring supportive care management.

Axatilimab, the most recently approved medication, works through a distinct mechanism as a fully humanized monoclonal antibody binding to CSF1R on activated monocytes and tissue macrophages. By inhibiting the CSF1/CSF1R pathway, axatilimab reduces inflammatory peptide secretion, particularly transforming growth factor beta, which leads to decreased fibrotic manifestations. The AGAVE 201 study tested three doses (0.3mg/kg every 2 weeks, 1mg/kg every 2 weeks, and 3mg/kg every 3 weeks) with remarkable results – 74% overall response rate in the 0.3mg/kg arm despite patients having advanced disease with a median GVHD duration of approximately 4 years.

The durability of response with axatilimab was particularly noteworthy, with 60% of patients remaining on the study drug at the one-year mark and median failure-free survival of 17.2 months. High organ-specific response rates were observed in the GI system, joints, and facial involvement (approximately 70% partial responses). Importantly, 40% of enrolled patients had lung involvement (bronchiolitis obliterans), with approximately 50% showing improvement in lung symptom scores or stabilization of pulmonary function testing – a significant finding given the typically poor response of lung GVHD to other treatments.