Clinical Trials in Graft-Versus-Host Disease: Changes in Study Characteristics, Investigated Drugs, and Endpoints Over Time.

BACKGROUND

Graft-versus-host disease (GvHD) remains a major complication of allogeneic hematopoietic cell transplantation (HCT). Mapping the trial landscape is essential to identify innovation barriers and optimize future study designs and trial conduct.

OBJECTIVES

This analysis characterized GvHD treatment trials registered on ClinicalTrials.gov to evaluate design features and results reporting trends.

RESULTS

Following screening of 1713 identified records, 384 trials met the specified inclusion criteria. Phase distribution was 15.9% phase 1, 38.8% phase 2, and 11.2% phase 3 studies. Single-group (61.1%) and parallel (31.3%) designs predominated, with sponsors being primarily academic (60.4%) or industry (30.7%). Regarding study status, 37.0% were completed, 22.9% prematurely halted, and 24.7% ongoing (15.4% unknown). For completed studies, the median number of participants was 30 and the median duration to reach the primary outcome was 3.13 years. Chronic GvHD was studied slightly more often (47.9%) than acute GvHD (43.5%), with significant differences in terms of study phases, recruitment status, duration, sponsor, and organ involvement. The most frequently studied treatments were corticosteroids (n = 64), mesenchymal stromal cells (n = 52), ruxolitinib (n = 31), extracorporeal photopheresis (n = 26), fecal microbiota transplantation (n = 17), rituximab (n = 15), and belumosudil (n = 13). The majority of trials (55.2%) investigated steroid-refractory GvHD or later-line treatment. Over the last decade, a significant shift toward industry sponsorship (13.4% to 38.9%, p < .001), multicenter designs, and targeted therapies was observed. Response was the predominant (60.1%) co-/primary endpoint of GvHD studies, followed by safety (28.2%), whereas patient-reported outcomes played a minor role (6.4%). Time to result reporting differed significantly based on trial phase and design.

CONCLUSIONS

While the trial landscape is evolving toward multinational collaborations and biology-based agents, the high rate of premature termination remains a substantial barrier to progress. Optimizing the study design, including regulatory advice, recruitment, and logistics, is critical to improve long-term outcomes in transplant recipients.