P147 | EFFICACY AND SAFETY OF BELUMOSUDIL AND EXTRACORPOREAL PHOTOPHERESIS COMBINATION THERAPY IN REFRACTORY CHRONIC GRAFT-VERSUS-HOST DISEASE: A SINGLE-CENTER RETROSPECTIVE STUDY

Background: Chronic GVHD, a major complication of allogeneic transplantation impacting quality of life even at low severity, is primarily managed with corticosteroids, though with suboptimal outcomes; emerging therapies such as belumosudil, a ROCK2 inhibitor, and ECP, particularly in combination, offer promising alternatives1. Aim and Methods: At our institution Fondazione Policlinico Gemelli between February 2024 and April 2025 we enrolled 7 patients, 5 females and 2 males with age 41 (25-64), with severe to moderate cGVHD (according to NIH grading system) refractory to at least two prior lines of therapy (median 4 lines). All patients received Belumosudil (400 mg daily for those on proton pump inhibitors, 200 mg for others) and ECP (two procedures per month, intensified to twice every two weeks in case of flare). Cytokine parameters (IL-2, IL-6, sST2) were assessed at therapy initiation and on the day of first ECP every month. Results: At belumosudil initiation, 5 patients had severe and 2 had moderate cGVHD, with treatment started for pulmonary (n=4), intestinal (n=2), and cutaneous (n=1) involvement. At belumosudil initiation, five patients remained on corticosteroids, one on ruxolitinib, three on cyclosporine, and one on mycophenolate mofetil. Median treatment duration was 7 months (range, 4–14). One patient discontinued therapy after 4 months due to disease progression and underwent lung transplantation; the remaining six continued treatment. Of these, two achieved a partial response at 12 months (severe to mild cGVHD) and discontinued immunosuppression, three maintained stable disease at 6 months with significant corticosteroid reduction, and one achieved a partial response at 3 months (severe to moderate cGVHD). The cGVHD Outcomes in our Patient Cohort at Last Follow-Up is represented in Figure 1. During the combination therapy we assisted to 3 infective episodes, two of them were severe with need of inpatient treatment. According to cytokine parameters, their levels did not exhibit a clear correlation with clinical response. Discussion: The Belumosudil and ECP combination was well tolerated, with no patients discontinuing due to intolerance. In our small cohort, this approach led to favorable clinical responses in heavily pre-treated patients. Larger studies with longer follow-up are needed to confirm the efficacy and safety of this therapy and to explore possible correlations between cytokine parameters and cGVHD progression. Olivieri A, Mancini G. Current Approaches for the Prevention and Treatment of Acute and Chronic GVHD. Cells. 2024 Sep 11;13(18):1524. doi: 10.3390/cells13181524