P776: ATGAM EFFICACY AND SAFETY IN MODERATE AND SEVERE ACQUIRED APLASTIC ANEMIA: OUTCOME OF A LARGE MULTICENTER COHORT OF 634 CHILDREN AND ADULTS FROM THE FRENCH AUTHORIZATION FOR TEMPORARY USE SURVEILLANCE PROGRAM

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Acquired aplastic anemia (AA) is a rare immunological disease resulting in bone marrow failure. Patients can be treated either by immunosuppressive therapy (IST) or by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT is the recommended treatment in patients younger than 40 years old with an available matched-related donor. IST is the recommended option for other patients: from the randomized trial published by Scheinberg in 2011, ATGAM® (horse anti-human T lymphocyte immunoglobulin) in addition to cyclosporine was the reference first-line IST for moderate to severe AA. Aims: This retrospective, multicentric study was conducted to report safety and efficacy data from ATGAM use in patients with AA utilizing surveillance data. Methods: This Temporary Use Authorization (ATU) program was initiated to collect surveillance data from the ATGAM Named Patients Program for French authorities before ATGAM was registered. This is the final report from this program. Safety and efficacy data was collected from the program and reported every 6 months. ATGAM was dosed at 40 mg/kg for 4 days in all patients that received treatment. Severity of AA was classified according to Camitta and EBMT scores. Response criteria followed the British Committee for Standards in Haematology Guidelines. For severe AA, no response: still severe; partial response: transfusion independence and the patient no longer met criteria for severe disease; complete response: hemoglobin was normal, neutrophil count >1.5x109/L, and platelet count >150x109/L. For moderate AA: no response: worse or did not meet criteria for response that included transfusion independence (if previously dependent) or doubling or normalization of at least 1 cell line or an increase of baseline hemoglobin, or an increase of baseline neutrophils or increase of baseline; complete response: the same criteria as for severe AA. Results: 634 patients (including 148 children) with moderate to very severe AA received ATGAM (n=537 first line; n=68 refractory/relapse; n=29 not classified) in addition to cyclosporine from January 2012 to August 2022. Overall hematologic response (Complete + Partial) at 6 months was 62.3% in the combined population. By severity, response rates were 84.4%, 50.8%, and 36.4% among patients with moderate, severe, and very severe AA, respectively, receiving first-line therapy (n=537; Table). By age, response rates were respectively 54.3%, 65.2%, and 64.4% in children (≤17 years), adults (≥18-<65 years), and elderly (≥65 years) patients. The overall survival rate (95% confidence interval) at 3 years was 96.9% (91.9-98.8%) in children, 83.4% (77.1-88.1%) in adults, and 79.7% (65.9-88.3%) in elderly patients. Treatment was well tolerated for the majority of patients. In total, 1087 adverse events (485 serious adverse events) were reported, with 48 fatal events. Summary/Conclusion: Reported response rate and overall survival in this real-life surveillance study are in line with a 2011 randomized controlled study comparing horse versus rabbit ATG (Scheinberg, et al [2011]) and control group of the most recent study RACE (Peffault de Latour, et al [2022]). The relatively large number of patients in this study compared with other similar studies in patients with AA adds to the robustness of this real-world data study. No new safety risks were identified, and this study showed that use of ATGAM remains favorable in this patient population.Keywords: ATG, Aplastic anemia, Immunosuppressive therapy