Abstract Rationale Chronic lung allograft dysfunction (CLAD) remains the leading cause of morbidity and mortality post-lung transplantation, characterized by persistent decline in lung function, typically defined by a ≥ 20% decrease in FEV1 from post-transplant baseline with exclusion of reversible causes. CLAD manifests predominantly as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS), both associated with poor long-term outcomes and limited effective treatment options. Belumosudil, an oral selective Rho-associated coiled-coil containing protein kinase 2 (ROCK2) inhibitor, has demonstrated efficacy in stabilizing lung function in steroid-refractory chronic graft-versus-host disease (cGVHD) with pulmonary involvement. Previous studies, including the ROCKstar and KD025-208 trials, have shown that belumosudil is generally well tolerated, with the most common adverse events reported as fatigue, gastrointestinal symptoms, dyspnea, liver enzyme elevations, and relatively few drug-related serious adverse events. While these findings support a favorable safety profile in cGVHD, the tolerability and adverse event profile of belumosudil in lung transplant recipients with CLAD remain underexplored. The purpose of this study is to retrospectively evaluate the safety of belumosudil in this population. Methods We conducted a single-center retrospective chart review of lung transplant recipients with CLAD initiated on belumosudil between January 2024 and June 2025. All documented adverse events were collected, with specific notation of whether each event led to drug discontinuation. Mortality during the study period was also collected. Results Among 39 patients, 56% reported no side effects. The most common adverse events were gastrointestinal (15%), including diarrhea, nausea, vomiting, GERD, and constipation. Other reported issues included dyspnea (5%), elevated liver function tests (3%), autonomic/motor symptoms (3%), weakness/fatigue (3%), and edema (3%). Overall, 8 patients (21%) discontinued the drug although it remains unclear whether these discontinuations were related to drug-associated side effects or effects from other medications. Median time to discontinuation of 51 days. Five patients died during the study period, including four from progressive respiratory failure one after a cardiac arrest of unclear etiology. The observed safety profile in this lung transplant cohort closely mirrored previously reported data in cGVHD populations, suggesting consistent tolerability across indications (Table 1). Conclusion In this retrospective cohort, belumosudil was well tolerated in lung transplant recipients with CLAD, with only a minority discontinuing therapy. No unexpected toxicities were observed. Five patients died during the study period. Overall, these findings suggest that belumosudil may be a feasible and safe therapeutic option in this high-risk population, providing a foundation for future studies to further explore its role in managing CLAD. This abstract is funded by: None
Moore et al. (Fri,) studied this question.