Later-Line and Combination Therapies in cGVHD and Future Directions

Segment 7 addresses third-line and later treatment strategies as the patient develops progressive sclerotic skin disease and new pulmonary involvement despite ruxolitinib. Dr. DeFilipp discusses FDA-approved options in this setting, particularly belumosudil, a ROCK2 inhibitor, and axatilimab, an anti-CSF1R monoclonal antibody. Both agents demonstrated response rates exceeding 70% in registrational trials and target inflammatory and fibrotic pathways relevant to advanced cGVHD.

The segment emphasizes that no head-to-head data are available to define a preferred agent, making route of administration, patient preference, prior therapies, and disease manifestations key determinants of choice. Oral convenience often favors belumosudil, whereas axatilimab may appeal to patients seeking to reduce pill burden.

Dr. DeFilipp also explores real-world use of combination strategies, noting that maintaining ruxolitinib while adding another agent may preserve partial benefit and avoid disease flare. He concludes by highlighting ongoing trials investigating earlier use of targeted agents, with the goal of reducing steroid dependence, preventing fibrosis, and fundamentally altering the long-term course of chronic GVHD.