In cGvHD treatment, a new approach involves selecting therapies based on their specific modes of action, aligned with the disease progression: inflammatory, immune deregulation, and fibrotic. For instance, drugs like ruxolitinib target inflammation, while belumosudil and axatilimab focus on combating fibrosis. Tailoring treatment based on the patient's clinical presentation and suspected pathogenesis optimizes effectiveness.

Previously, minimizing the number of immunosuppressive drugs was a key principle in cGvHD management. However, with the introduction of newer targeted drugs, a combination strategy is now being reconsidered. This approach may involve pairing a novel agent like ruxolitinib or belumosudil with another extensively evaluated therapeutic agent.

There's a pressing need for the development of a corticosteroid-free front-line regimen in cGvHD treatment. Corticosteroids have been the primary treatment for over five decades. Where possible, clinical trials of initial systemic therapy should prioritize investigating steroid-free therapeutic approaches in front-line treatment.

Adopting a pre-emptive treatment approach could be optimal for enhancing the quality of life and long-term outcomes in patients with highly morbid forms of cGvHD. This strategy has the potential to halt the progression of cGvHD in high-risk individuals who are likely to develop severe and debilitating forms of the disease. Implementing this approach may necessitate additional research into biomarker development for cGvHD.