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. 2025 Jan 14;9(1):29-38.
doi: 10.1182/bloodadvances.2024014104.

Gene therapy in transfusion-dependent non-β0/β0 genotype β-thalassemia: first real-world experience of beti-cel

Adil Mirza  1 , Mona-Lisa Ritsert  1 , Gloria Tao  2 , Himal Thakar  2 , Stephan Lobitz  3 , Sabine Heine  4 , Leila Koscher  5 , Matthias Dürken  6 , Anita Schmitt  7 , Michael Schmitt  7 , Petra Pavel  8 , Sascha Laier  8 , Donate Jakoby  1 , Johann Greil  1 , Joachim Kunz  1 , Andreas Kulozik  1   9
Affiliations

Gene therapy in transfusion-dependent non-β0/β0 genotype β-thalassemia: first real-world experience of beti-cel

Adil Mirza et al. Blood Adv. .

Abstract

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, to our knowledge, 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≥12 years without a β0/β0 genotype and without a HLA-matched sibling donor, before beti-cel marketing authorization was withdrawn by its holder because of nonsafety reasons.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 after 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 because of 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.

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Conflict of interest statement

Conflict-of-interest disclosure: A.K. received research support and royalties from bluebird bio, Inc. H.T. and G.T. are employees of, and hold stock/stock options in, bluebird bio. J.K. is a consultant for bluebird bio, Vertex, Novartis, and Pfizer, and receives research support from Pfizer, Novo Nordisk, Novartis, and Deutsche Kinderkrebsstiftung. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
RBC transfusion requirement of 8 patients after beti-cel infusion.
Figure 2.
Figure 2.
Kinetics of Hb levels and platelet counts in 8 TDT patients after beti-cel infusion.
Figure 3.
Figure 3.
Hb and HbAT87Q at months 6, 12, and 24.
See this image and copyright information in PMC

References

    1. Taher AT, Musallam KM, Cappellini MD. β-Thalassemias. N Engl J Med. 2021;384(8):727–743. - PubMed
    1. Thein SL. Pathophysiology of beta thalassemia--a guide to molecular therapies. Hematology Am Soc Hematol Educ Program. 2005;2005(1):31–37. - PubMed
    1. Scalone L, Mantovani LG, Krol M, et al. Costs, quality of life, treatment satisfaction and compliance in patients with β-thalassemia major undergoing iron chelation therapy: the ITHACA study. Curr Med Res Opin. 2008;24(7):1905–1917. - PubMed
    1. Sobota A, Yamashita R, Xu Y, et al. Quality of life in thalassemia: a comparison of SF-36 results from the thalassemia longitudinal cohort to reported literature and the US norms. Am J Hematol. 2011;86(1):92–95. - PMC - PubMed
    1. Yengil E, Acipayam C, Kokacya MH, Kurhan F, Oktay G, Ozer C. Anxiety, depression and quality of life in patients with beta thalassemia major and their caregivers. Int J Clin Exp Med. 2014;7(8):2165–2172. - PMC - PubMed