P075 | ERYTHROID STIMULATING AGENTS IN VEXAS SYNDROME: A MULTICENTER RETROSPECTIVE STUDY OF AN ITALIAN VEXAS COHORT

Background: VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an autoinflammatory disorder caused by UBA1 mutation. It manifests with inflammatory symptoms and commonly macrocytic anemia, which in up to 50% of cases meets WHO 2022 criteria for Myelodysplastic Neoplasia. Such anemia is believed to be related both to inflammation and early erythroblast mortality, and has no standard therapy beside transfusions, which cause iron overload and impaired quality of life. Aims: to analyse the efficacy and safety of erythropoiesis stimulating agents (ESAs) in VEXAS patients. Methods: an electronic survey was emailed to centers managing VEXAS patients. All patients with confirmed VEXAS by UBA1 testing who received ESA were included. Cytopenias and MDS were classified as per WHO 2022 and stratified by IPSS-R and IPSS-M. Response was evaluated with IWG 2018 response criteria. UBA1 VAF was determined by digital droplet PCR. Results: 32 male patients affected by VEXAS syndrome received ESAs at 13 canters for symptomatic anemia. At baseline 63% of them were transfusion-dependent (n=13 low transfusion burden; n=7 high transfusion burden); 82% had concomitant MDS, mostly low risk. HI-E to ESAs was achieved in 59%, and correlated with lower endogenous erythropoietin levels [OR 0.985 (95%CI=0.972 – 0.999), p=0.033]. Median duration of response was 13 months. 6 responders (31%) lost response after a median of 14 months. UBA1 VAF remained stable compared to baseline, consistently with the evidence that only clone-targeting therapies as azacitidine or allogeneic hematopoietic cell transplantation impact UBA1 burden. After ESA discontinuation, 53% of patients received clone-suppressing therapies, 18% bDMARDS, 24% supportive therapy. During ESAs treatment, only 4 patients experienced deep vein thrombosis (21%). With a median follow up of 22.8 months, 24 patients were still alive (75%). Of 8 deaths, 7 occurred in patients who either lost or never achieved a response, and were transfusion-dependent at the time of ESAs discontinuation. Summary/Conclusion: This study confirms that ESAs are effective and safe in VEXAS patients. Prospective studies are needed to confirm our retrospective findings and to explore the use of therapies such as Luspatercept, approved for anemia in low-risk MDS, to identify optimal anemia treatment for these patients.