Abstract
Purpose :
Cancer patients who undergo stem cell transplants are at significant risk for developing Graft versus Host Disease (GVHD) and its ocular manifestation (oGVHD). Treatments for oGVHD, which presents as painful and severe dry eye disease, are limited and tend to be inadequate in achieving remission. We performed a retrospective, observational study to investigate if Belumosudil (Rezurock), a selective Rho-kinase 2 (ROCK2) inhibitor improved the clinical evaluations of oGVHD patients. Belumosudil reduces inflammation by decreasing ROCK2-induced STAT3 activity, which upregulates pro-inflammatory T helper 17 and follicular helper cells. It also decreases fibrosis by preventing actin polymerization and profibrotic gene transcription. ROCK2 is expressed by corneal epithelial cells, suggesting Belumosudil’s potential use for targeted oGVHD treatment. We hypothesize that patients on Belumosudil will have a clinically meaningful improvement in their oGVHD and will have a correlative improvement in their tear cytokine profile.
Methods :
This study aims to analyze the impact of Belumosudil on oGVHD patients (n=3) seen at the University of Maryland Medical Center. Through a chart review, we evaluated dry eye symptoms with the Ocular Surface Disease Index, tear production via the Schirmer's Test, and pain with the Ocular Discomfort Scale. Patients were compared to matched oGVHD non-treated controls. We performed cytokine tear analysis with the Luminex assay to correlate changes with clinical findings.
Results :
Our clinical findings show no difference between patient groups. However, there was some individual improvement during Belumosudil treatment (see Table 1). Cytokine tear profiling showed an inverse relationship between length of treatment and levels of macrophage inflammatory protein (MIP) -1alpha and MIP-1beta, which increase with inflammation (see Table 2).
Conclusions :
Our results suggest that Belumosudil may help the eyes of patients with oGVHD. Our limitations included a small sample size, lack of some visit notes, and the likelihood of treated patients having more severe oGVHD than the controls. However, future studies with larger cohorts are needed to better understand its therapeutic use for the oGVHD population.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.