DP102 | THE IMPACT OF RUXOLITINIB ON STEROID-REFRACTORY CGVHD: ASSESSING CUTANEOUS RESPONSES AND LONG-TERM PROGNOSTIC FACTORS ACROSS PHENOTYPES

Background: Chronic Graft-Versus-Host Disease (cGVHD) is a prevalent and debilitating complication of allogeneic stem cell transplantation. Skin involvement is a common concern and a potential key prognostic factor that influences patients' quality of life (QoL). Although the efficacy of Ruxolitinib in steroid-refractory cGVHD has been well documented, its specific effects on cutaneous manifestations and its impact on patient-reported symptom burden are still poorly elucidated. Methods: This observational study involved 44 patients with cGVHD who had failed prior treatments and presented with skin manifestations before initiating Ruxolitinib therapy. Patients were divided into three subgroups based on their skin characteristics: epidermal, sclerodermic, or combined. The response of skin involvement and the impact of Ruxolitinib on QoL were evaluated at 3 and 6 months using the NIH skin score and the Lee Symptom Scale (LSS). Results: Of the 44 patients, 11 had epidermal-type cGVHD, 10 had sclerodermic-type, and 23 had combined-type. There were no significant differences between the groups regarding sex, age, number of prior treatments and cGVHD classification. However, significant differences were observed in the distribution of overlap and classic forms (p=0.001), with overlap cGVHD being more prevalent in the epidermal group (EG), and classic cGVHD more common in the sclerodermic group (SG). The median time from cGVHD diagnosis to Ruxolitinib treatment was significantly shorter for the EG (263 days) compared to the SG (892 days) and CG (607 days). At 3 months, the overall response was significantly better in the EG (p=0.0187). At 6 months, the overall response was similar across all groups (p=0.3). The skin-specific response at 3 months, as measured by the NIH score, was significantly better in the epidermal group (p=0.0013). This improvement in skin response persisted at 6 months, with the EG showing the most significant response (p=0.0009). Notably, at 3 months the NIH clinical response correlates with a significant improvement in the LSS, particularly in the EG (p=0.0088). No significant change in LSS is observed at 6 months. In terms of toxicities, no grade 3-4 infections were reported, but 7 patients developed secondary cancers after Ruxolitinib treatment (including 5 non-melanoma skin cancers) at a median time from Ruxolitinib introduction of 57 months (range 19-85). Additionally, the 5-year overall survival (OS) was similar across all groups and there were no significant differences in 2-year and 5-year event-free survival (EFS) with a trend towards better EFS in the EG compared to the other groups. Conclusions: This observational study demonstrates the efficacy of Ruxolitinib in treating skin manifestations of steroid-refractory cGVHD, with epidermal cutaneous forms showing a more favourable early-response. Notably, patients with epidermal-type cGVHD experienced more frequently an overlap form with a shorter time from diagnosis to treatment initiation, along with significantly better skin responses at both 3 and 6 months and an important change in LSS at 3 months, indicating an improvement in their QoL. These results represent a change from previously reported pre-Ruxolitinib case series that showed a worse outcome in epidermal and overlap forms. An accurate surveillance for skin-cancer is recommended as part of the follow-up at any time.