Third-Line Options: Targeting Fibrosis and Pulmonary cGVHD

Dr. Shune concludes the discussion by focusing on safety, sequencing, and practical considerations for incorporating axatilimab into the cGVHD treatment paradigm. She notes that data from the AGAVE-201 trial demonstrated both efficacy and a favorable safety profile for axatilimab, which has been corroborated by emerging real-world experience presented at ASH. In these real-world analyses, axatilimab showed safety and discontinuation rates comparable to those observed in clinical trials, allowing patients to remain on therapy for extended periods.

With multiple FDA-approved options now available in later lines of therapy, Dr. Shune explains her evolving approach to sequencing. Although she initially used axatilimab primarily in the third-line setting, she has increasingly considered earlier use in patients with high-risk features, including sclerotic skin disease, pulmonary involvement, and ocular or oral GVHD. She cites its relatively rapid onset of action, good tolerability, and ability to be combined with other systemic agents as key advantages. By targeting the CSF1 receptor and inhibiting monocyte–macrophage-driven fibrotic pathways, axatilimab may offer an opportunity to intervene earlier in sclerotic disease with the goal of preserving or recovering organ function.

Patient preference also plays a central role in treatment selection. Dr. Shune contrasts oral options, such as belumosudil, with axatilimab’s intravenous administration every 2 weeks, noting that some patients prioritize convenience while others are comfortable with infusions. Axatilimab is associated with minimal infusion-related reactions, and dosing intervals may be extended to every 4 weeks in responding patients. She also highlights the feasibility of transitioning infusions to community centers, given clinicians’ familiarity with monoclonal antibody therapies.

Finally, Dr. Shune emphasizes the importance of leveraging complementary mechanisms of action across available therapies, including JAK, ROCK, BTK, and CSF1 receptor inhibition. Real-world expanded access data suggest these agents can be safely combined, supporting an additive, mechanism-driven approach to future cGVHD management.