Analysis of the Impact of Body Mass Index (BMI) on the Durability of Response in Patients with Aplastic Anemia Treated with Weight-Adjusted Horse Anti-Thymocyte Globulin (hATG)

Introduction: Immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG), cyclosporine A (CsA) and Eltrombopag (Epag) has recently been established as standard of care in adult patients (pts.) with severe (sAA) or very severe (vsAA) aplastic anemia > 40-50 years or ineligible for transplant for other reasons. ATG works via immunosuppressive properties including T-cell depletion and induction of immune tolerance. Horse ATG (hATG) is applied for 4 days with 40 mg/kg/day based on the patient's current body weight. Thus, obese pts., defined by a body mass index (BMI) ≥ 30, receive higher absolute hATG dosages than non-obese pts. (BMI < 30). To date, it is unknown whether increased hATG dosages in obese pts. might have beneficial or adverse effects on AA treatment. To address the role of obesity in AA, we investigated (1) the prevalence of obesity in 334 pts. with (suspected) AA and (2) compared the overall survival (OS) and response of 89 obese and non-obese AA pts. to the treatment with hATG/CsA ±Epag. Methods: Retrospective analysis of data from pts. enrolled in the German Registry for Aplastic Anemia and Bone Marrow Failure (AA-BMF). 334 pts. with (suspected) AA and available BMI data (49% (n=164) male/ 51% (n=170) female, 83% (n=278) BMI < 30, 17% (n=56) BMI ≥ 30) were identified of which 89 pts. (43 male/ 46 female, mean age 50 ± 17 years, 75 BMI < 30/ 14 BMI ≥ 30 at hATG administration) with confirmed diagnosis of AA (4 mAA/ 49 sAA/ 18 vsAA/ 14 AA not otherwise specified/ 4 AA-PNH Overlap) and treatment with hATG/CSA were analyzed in detail. 14 pts. received hATG/CSA/Epag (all BMI < 30). Follow-up data were compiled over 35 ± 38.5 months between 2000 and 2023, whereby follow-up data of 12 pts. were incomplete. Results are given as mean ± standard deviation. Results: Analysis of the age distribution of the 343 pts. with (suspected) AA showed a mean age of 50 ±17 years with a biphasic peak at age approx. 25 and 65 years. The average BMI stratified by age (20-30y: 22.9, 31-40y: 24.5, 41-50y: 26.8, 51-60y: 26.4, 61-70y: 27.5, >70y: 27.8) corresponded to the BMI distribution of the German population surveyed by the German Federal Statistical Office. In accordance with the expected survival rates, the 89 AA pts. treated with hATG/CSA (including 14 pts. with Epag) revealed a 5-year overall survival (OS) of 93%/ 86%/ 67 % at < 40/ 40-60/ > 60 years. Regarding BMI, no significant difference was observed in 5-year OS between obese (BMI ≥ 30, 5y-OS 67%) and