TY  - JOUR
AU  - Mirza, Adil
AU  - Ritsert, Mona-Lisa
AU  - Tao, Gloria
AU  - Thakar, Himal
AU  - Lobitz, Stephan
AU  - Heine, Sabine
AU  - Koscher, Leila
AU  - Dürken, Matthias
AU  - Schmitt, Anita
AU  - Schmitt, Michael
AU  - Pavel, Petra
AU  - Laier, Sascha
AU  - Jakoby, Donate
AU  - Greil, Johann
AU  - Kunz, Joachim B
AU  - Kulozik, Andreas
TI  - Gene Therapy in Transfusion-Dependent Non-β0/β0 Genotype β-Thalassemia: First Real-World Experience of Beti-cel.
JO  - Blood advances
VL  - 9
IS  - 1
SN  - 2473-9529
CY  - Washington, DC
PB  - American Society of Hematology
M1  - DKFZ-2024-02097
SP  - 29-38
PY  - 2025
N1  - #LA:A400# / 2025 Jan 14;9(1):29-38
AB  - 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genotype and without a human leukocyte antigen (HLA)-matched sibling donor, before beti-cel marketing authorization was withdrawn by its holder due to non-safety reasons.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.
LB  - PUB:(DE-HGF)16
C6  - pmid:39418614
DO  - DOI:10.1182/bloodadvances.2024014104
UR  - https://inrepo02.dkfz.de/record/294076
ER  -