Future Directions: Combination Strategies and Earlier Intervention for cGVHD

Dr. Shune discusses how practical considerations such as monitoring requirements, route of administration, and patient preference are integrated into treatment decision-making for patients with progressive, multi-organ cGVHD, particularly in later lines of therapy. She emphasizes the importance of shared decision-making, outlining for patients the mechanisms of action, clinical trial data, and expected response rates of available agents, including axatilimab based on AGAVE-201 and belumosudil based on the ROCKstar trial. Although patient preference regarding oral versus intravenous therapy plays a meaningful role, disease phenotype ultimately influences treatment selection, especially in patients with worsening sclerosis or pulmonary involvement, where therapies targeting fibrotic pathways may be prioritized to arrest disease progression and potentially reverse organ damage.

Dr. Shune highlights that the growing availability of FDA-approved agents with distinct and complementary mechanisms has transformed cGVHD management. The ability to combine therapies targeting different immune pathways (innate and adaptive) offers new opportunities to address severe manifestations, particularly sclerotic skin and lung disease, which have historically been difficult to treat. She underscores the value of having multiple therapeutic options available to tailor treatment strategies to individual patient needs and disease trajectories.

Looking ahead, Dr. Shune expresses optimism about ongoing and future clinical trials that aim to move effective therapies earlier in the cGVHD treatment course. She notes particular interest in studies evaluating axatilimab earlier in disease and in comparative or combination approaches with agents such as ruxolitinib. These trials are expected to clarify optimal sequencing and combination strategies and may help prevent irreversible organ damage by intervening sooner.

Finally, she discusses future directions focused on reducing treatment burden, including alternative methods of delivering CSF1 receptor-targeted therapies. Potential advances include less frequent dosing, home or community-based infusions, subcutaneous formulations, or even oral small molecules. Such innovations could improve accessibility and quality of life for patients while expanding the impact of antifibrotic strategies across cGVHD and other fibrotic lung diseases.