Correlation of Patient-Reported Outcomes with Clinical Organ Responses: Data from the Belumosudil Chronic Graft-versus-Host Disease Studies.

Chronic graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT) owing to both the disease itself and the immunosuppressive agents used for treatment. Response criteria endorsed by the National Institutes of Health (NIH) Consensus Conference on Clinical Trials in chronic GVHD include both clinician-documented measures and patient-reported outcomes (PROs) since both are considered clinical benefits by the Food and Drug Administration. The correlation between clinically assessed responses in organs and PRO improvements in organ-specific symptoms has not been investigated in depth. We used data from 2 published studies of belumosudil, an oral rho-associated coiled-coil-containing protein kinase-2 (ROCK2) inhibitor, for chronic GVHD to test the correlation between clinical and PRO outcomes. Participants completed PROs at enrollment and every 1 to 2 cycles according to the study design. Individual organ responses (complete plus partial response) and clinically meaningful changes in PROs were defined according to published methods. Generalized estimating equation methods were used to correlate changes in PROs associated with clinical responses according to NIH criteria, accounting for missing information and repeated measures. Data from all doses in both trials were included without stratification. The liver and genital tract were not included owing to a lack of site-specific PROs. Our pooled analysis of clinical and PRO data included 170 patients enrolled in 2 belumosudil studies (NCT02841995, n = 54; NCT03640481, n = 132) for whom we had baseline PROs, at least 1 follow-up PRO, and at least 1 response assessment. There was a strong positive correlation between complete and partial organ and overall responses and changes in PRO symptom scores, as well as clinically meaningful improvements. For all organs except joints, esophagus, and lower gastrointestinal tract, there was at least 1 PRO statistically correlated with NIH organ response. These data support the use of PROs for response assessment to document clinically meaningful benefit in chronic GVHD clinical trials.