%0 Journal Article
%A Mirza, Adil
%A Ritsert, Mona-Lisa
%A Tao, Gloria
%A Thakar, Himal
%A Lobitz, Stephan
%A Heine, Sabine
%A Koscher, Leila
%A Dürken, Matthias
%A Schmitt, Anita
%A Schmitt, Michael
%A Pavel, Petra
%A Laier, Sascha
%A Jakoby, Donate
%A Greil, Johann
%A Kunz, Joachim B
%A Kulozik, Andreas
%T Gene Therapy in Transfusion-Dependent Non-β0/β0 Genotype β-Thalassemia: First Real-World Experience of Beti-cel.
%J Blood advances
%V 9
%N 1
%@ 2473-9529
%C Washington, DC
%I American Society of Hematology
%M DKFZ-2024-02097
%P 29-38
%D 2025
%Z #LA:A400# / 2025 Jan 14;9(1):29-38
%X Gene addition and editing strategies for transfusion-dependent β-thalassemia have gained momentum as potentially curative treatment options, with studies showcasing their efficacy and safety. We report the first real-world application of betibeglogene autotemcel (beti-cel; ZYNTEGLO™) during its period of active license in Europe from January 2020 to March 2022 for patients aged ≥ 12 years without a β0/β0 genotype and without a human leukocyte antigen (HLA)-matched sibling donor, before beti-cel marketing authorization was withdrawn by its holder due to non-safety reasons. Among 15 screened patients, 4 opted out for fertility and safety concerns, 2 were excluded because of marked hepatic siderosis, and 1 had apheresis collection failure. Eight patients received beti-cel post busulfan myeloablative conditioning, all achieving transfusion independence within 8 to 59 days with posttreatment hemoglobin levels ranging from 11.3 to 19.3 g/dL. No deaths occurred, but acute toxicity mirrored busulfan's known effects. Posttreatment platelet management faced challenges due to HLA-antibodies in 3 patients. Monitoring up to Month 24 revealed pituitary-gonadal endocrine dysfunction in all 3 female and in 2 of 5 male patients. Additionally, we observed unexpected posttreatment sequelae: 1 patient developed polycythemia that could not be explained by known genetic or acquired mechanisms, 1 patient developed posttreatment depression and anxiety prohibiting her from returning to work, and 1 patient developed fatigue severely compromising both quality of life and work capacity. This real-world experience corroborates beti-cel's efficacy and safety and provides information on adverse events observed during real-world use of the therapy.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39418614
%R 10.1182/bloodadvances.2024014104
%U https://inrepo02.dkfz.de/record/294076