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 non-obese pts. (BMI < 30, 5y-OS 85%, p = 0.51). In pts. responding to IST, hematological response at six months after ATG was reached in 67 % (n=7/11) of the obese and 63 % (n=21/33, in 9 pts. exact timepoint not available) of the non-obese pts. (p = 0.85). The proportion of primary IST refractory pts. was numerically lower in obese (21 %, n=3/14) than in non-obese pts. (32 %, n=21/65, p=0.53). Among all 53 responders (2 pts. had incomplete follow-up to assess relapse), a significantly lower relapse rate of 9 % (n=1/11) in obese (median follow-up: 16 months, range 3 to 120 months) compared to 55 % (n=22/40) in non-obese pts. was observed (median follow-up: 19 months, range 1 to 87 months, p=0.008).

Conclusion: BMI distribution of AA pts. by age is comparable to that of the general population with a higher rate of obesity in older pts.. Pts. with a BMI ≥ 30 thus receiving higher ATG dosages do appear to have comparable OS and hematological response rates compared to pts. with BMI <30. However, pending validation in a larger patient cohort, we hypothesize, based on our analysis, that a higher cumulative total ATG dose may have a beneficial impact on relapse rates in pts. with BMI ≥ 30 compared to those with BMI < 30.

Walter:Gilead Sciences: Other: Travel allowance. Theis:Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SOBI: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees. Hansmann:Amgen: Other: Travel expenses; Sanofi: Membership on an entity's Board of Directors or advisory committees. Radsak:Bristol Myers Squibb: Consultancy, Honoraria, Other: Travel support; Novartis: Consultancy, Honoraria, Other: Travel support; Takeda: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Corat: Consultancy, Honoraria; Cogent Biosciences: Consultancy, Honoraria; TEVA: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel support; Pfizer: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Glaxo Smith Kline: Consultancy, Honoraria; JAZZ: Other: Travel support; Daiichi Sankyo: Other: Travel support; Amgen: Other: Travel support; Astellas: Other: Travel support; SOBI: Other: Travel support; AOP: Other: Travel support. Heuser:PinotBio: Consultancy, Research Funding; Novartis: Honoraria; Pfizer: Consultancy, Honoraria; Certara: Honoraria; Sobi: Honoraria; Servier: Consultancy; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Karyopharm: Research Funding; Loxo Oncology: Research Funding; Glycostem: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; BergenBio: Research Funding; Astellas: Research Funding; Agios: Research Funding; Abbvie: Consultancy, Research Funding; Amgen: Consultancy; LabDelbert: Consultancy. Chromik:Alexion: Honoraria. Schubert:Alexion: Honoraria. Isfort:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; BMS: Honoraria; AOP Orphan: Honoraria, Other: Travel support; Alexion: Other: Travel support; Mundipharma: Other: Travel support; Roche: Other: Travel support; Hexal: Other: Travel support. Panse:Alexion, AstraZeneca Rare Disease: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy; BMS: Consultancy; Sanofi Ltd: Consultancy; Apellis Pharmaceuticals, Inc.: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Blueprint Medicines: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SOBI: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Samsung Bioepis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; F. Hoffmann-La Roche Ltd,: Membership on an entity's Board of Directors or advisory committees, Other: Third party writing assistance by Akshaya Srinivasan, PhD, of MediTech Media Ltd and funded by F. Hoffmann-La Roche Ltd, , Speakers Bureau; Amgen: Consultancy. Brümmendorf:Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Speakers Bureau. Beier:Alexion: Honoraria, Speakers Bureau; Gilead: Honoraria; Sobi: Honoraria; Novartis: Honoraria; Pfizer: Honoraria, Other: Travel support, Speakers Bureau.

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2023
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