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@ARTICLE{Kwiatkowski:307629,
author = {J. L. Kwiatkowski and A. A. Thompson and J. Schneiderman
and I. Thuret and A. Kulozik$^*$ and E. Yannaki and M.
Cavazzana and S. Hongeng and T. S. Olson and M. G. Sauer and
A. J. Thrasher and A. Lal and J. E. Rasko and J. B. Kunz and
M. A. Kinney and A. Chawla and S. Ali and G. Tao and H.
Thakar and C. Paramore and N. Witthuhn and M. C. Walters and
F. Locatelli},
title = {{L}ong-term efficacy and safety results of betibeglogene
autotemcel gene therapy for transfusion-dependent
β-thalassemia.},
journal = {Blood},
volume = {nn},
issn = {0006-4971},
address = {Washington, DC},
publisher = {American Society of Hematology},
reportid = {DKFZ-2026-00101},
pages = {nn},
year = {2026},
note = {epub},
abstract = {Betibeglogene autotemcel (beti-cel) gene therapy for
transfusion-dependent β-thalassemia (TDT) involves
autologous transplantation of hematopoietic stem and
progenitor cells transduced with a modified β-globin gene
to produce functional adult hemoglobin (HbAT87Q).
Sixty-three participants with TDT (median [range] age: 17
[4-35] years) received beti-cel in phase 1/2 (n = 22) or
phase 3 (n = 41) studies and enrolled in the long-term
follow-up LTF-303 study (clinicaltrials.gov/NCT02633943;
median [range] follow-up: 5.9 [2.9-10.1] years).
Manufacturing refinements in phase 3 increased transduction
efficiency, resulting in higher drug product vector copy
number and HbAT87Q levels, which translated into higher
hemoglobin and transfusion independence (TI) rates compared
with phase 1/2. TI was achieved by $68.2\%$ (15/22) of phase
1/2 participants (median weighted average Hb during TI, 10.2
g/dL) and $90.2\%$ (37/41) of phase 3 participants (median,
11.2 g/dL) and was sustained through last follow-up.
Treatment efficacy was similar across ages and TDT
genotypes. Among participants achieving TI, $73\%$ (38/52)
had discontinued iron chelation at last follow-up, with no
increase in liver iron concentration. Markers of ineffective
erythropoiesis, including serum transferrin receptor and
erythropoietin, improved with restoration of iron
homeostasis. Health-related quality-of-life assessment
scores showed durable improvements. No malignancies,
insertional oncogenesis, or vector-derived
replication-competent lentivirus were reported. These
findings establish beti-cel as a durable, one-time therapy
that achieves TI, restores iron balance, and improves
quality of life, offering a potentially curative treatment
option for people with TDT.},
cin = {A400},
ddc = {610},
cid = {I:(DE-He78)A400-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41525466},
doi = {10.1182/blood.2025029196},
url = {https://inrepo02.dkfz.de/record/307629},
}