TY  - JOUR
AU  - Kwiatkowski, Janet L
AU  - Walters, Mark C
AU  - Hongeng, Suradej
AU  - Yannaki, Evangelia
AU  - Kulozik, Andreas
AU  - Kunz, Joachim B
AU  - Sauer, Martin G
AU  - Thrasher, Adrian J
AU  - Thuret, Isabelle
AU  - Lal, Ashutosh
AU  - Tao, Ge
AU  - Ali, Shamshad
AU  - Thakar, Himal L
AU  - Elliot, Heidi
AU  - Lodaya, Ankit
AU  - Lee, Ji
AU  - Colvin, Richard A
AU  - Locatelli, Franco
AU  - Thompson, Alexis A
TI  - Betibeglogene autotemcel gene therapy in patients with transfusion-dependent, severe genotype β-thalassaemia (HGB-212): a non-randomised, multicentre, single-arm, open-label, single-dose, phase 3 trial.
JO  - The lancet
VL  - 404
IS  - 10468
SN  - 0140-6736
CY  - London [u.a.]
PB  - Elsevier
M1  - DKFZ-2024-02457
SP  - 2175 - 2186
PY  - 2024
AB  - Transfusion-dependent β-thalassaemia (TDT) is a severe disease, resulting in lifelong blood transfusions, iron overload, and associated complications. Betibeglogene autotemcel (beti-cel) gene therapy uses autologous haematopoietic stem and progenitor cells (HSPCs) transduced with BB305 lentiviral vector to enable transfusion independence.HGB-212 was a non-randomised, multicentre, single-arm, open-label, phase 3 study of beti-cel in patients with TDT conducted at eight centres in France, Germany, Greece, Italy, the UK, and the USA. Patients with β0/β0, β0/β+IVS-I-110, or β+IVS-I-110/β+IVS-I-110 genotypes, clinically stable TDT, and a transfusion history of at least 100 mL/kg per year of packed red blood cells (pRBCs) or at least eight transfusions of pRBCs per year in the 2 years before enrolment were eligible for participation. After undergoing HSPC mobilisation and busulfan-based, pharmacokinetic-adjusted myeloablative conditioning, patients were infused with beti-cel and followed up for 24 months. The primary efficacy outcome was transfusion independence, defined as weighted average haemoglobin level of 9 g/dL or above without pRBC transfusions for 12 or more months. The primary outcome was measured in all patients who received an infusion of beti-cel (transplant population); safety was evaluated in all patients who initiated study treatment (intention-to-treat population). Patients were eligible to enrol in the ongoing 13-year long-term follow-up study (for a total of 15 years), LTF-303 (registered at ClinicalTrials.gov, NCT02633943). This trial, HGB-212, was registered at ClinicalTrials.gov (NCT03207009), and is complete.From June 8, 2017, to March 12, 2020, 20 patients were screened for eligibility. One patient was ineligible and one withdrew consent before HSPC mobilisation and myeloablative conditioning. Of the 18 patients who received beti-cel, ten (56
LB  - PUB:(DE-HGF)16
C6  - pmid:39527960
DO  - DOI:10.1016/S0140-6736(24)01884-1
UR  - https://inrepo02.dkfz.de/record/294724
ER  -