Organ-Specific Responses to cGVHD Therapies Highlight Need for Tailored Treatment and Better Metrics

A new systematic review of 20 studies reports variable organ-specific treatment response rates to second- and subsequent-line therapies for chronic graft vs host disease (cGVHD), providing clinicians with updated evidence to guide therapeutic selection in patients refractory to systemic corticosteroids.

The review analyzed studies on 5 major agents: ruxolitinib, ibrutinib, belumosudil, axatilimab, and extracorporeal photopheresis. Researchers then calculated pooled response rates for key target organs, including skin, liver, lung, joints, and gastrointestinal tract. Ruxolitinib was the most frequently studied, with 8 reports included.

Notably, skin response rates varied widely, and discrepancies were observed between objective criteria and patient-reported improvements in sclerotic manifestations. 

“We observed large discrepancies in organ response rates according to the current NIH criteria and patient-reported improvement, highlighting the need for better measurement tools,” the authors stated.

Response patterns varied by agent. Ibrutinib showed the highest organ-specific efficacy in the liver (71%) and gastrointestinal tract (81%), possibly reflecting its immune-modulating effects on B cells. Belumosudil demonstrated high response rates in the joints and fascia (up to 80%), aligning with its role in modulating fibrosis. Ruxolitinib had broad organ coverage, though with low lung response rates in prospective trials. Axatilimab showed favorable results in the gastrointestinal tract (93%) and promising lung responses, suggesting potential for early intervention.

Despite improved study quality compared to earlier research, the review underscores the limitations of current data. Baseline disease severity, response definitions, and lack of standardized measurement tools limit comparability. 

“Information regarding the expected response rate in individual organs may help the drug choice for patients with refractory chronic GVHD,” the study concluded.

Future research directions include developing objective measures for cutaneous sclerosis, refining ocular GVHD scoring, and exploring combination therapies such as ruxolitinib and axatilimab. This organ-level evidence may support more precise, mechanism-based treatment selection in clinical practice.

Reference 
Morishita T, Martin PJ, Inamoto Y. Treatment response in individual organs affected by chronic graft-versus-host disease. Cells. 2025; 14(4):238. doi: 10.3390/cells14040238