The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Hematology Advisor‘s conference coverage.

An interim analysis of data from LTF-303 ( Identifier: NCT02633943), a 13-year follow-up study of patients with transfusion-dependent β-thalassemia (TDT) who received betibeglogene autotemcel (beti-cel) gene therapy, demonstrated durability and stability of response with up to 6 years of follow up.

The findings were presented by Janet L. Kwiatkowski, MD, MSCE, of the Children’s Hospital of Philadelphia and Perelman School of Medicine of the University of Pennsylvania in Philadelphia, at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

Of 60 patients treated to date, the study includes all 32 patients treated with beti-cel who completed 4 parent studies (2 completed phase 1/2 [HGB-204, HGB-205] and 2 ongoing phase 3 studies [HGB-207, HGB-212]). After 2 years of follow-up in these studies, patients could then enroll in LTF-303 for long-term follow up, with assessments every 6 months for 3 years and then annually.

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The investigators assessed numerous variables and outcomes, including transfusion independence (TI; defined as a weighted average Hb ≥9 g/dL without packed red blood cell transfusions for ≥12 months), hemoglobin (Hb), peripheral blood vector copy number, markers of erythropoiesis, iron overload, quality of life, adverse events (AEs), replication-competent lentivirus (RCL), and vector insertion sites.

For the 32 patients,  the median age at enrollment in the parent studies was 20 years (range, 12 to 35 years), and 22 of these patients were treated in the phase 1/2 studies while 10 were treated in the phase 3 studies. After gene therapy, the median follow-up was 49.1 months (range, 23.3 to 71.8 months).

The vector copy number (3.2 vs 0.8 copies/diploid genome, respectively) and the percent transduced CD34+ cells (82% vs 32%, respectively) was significantly higher in patients in the phase 3 studies compared with those in the phase 1/2 studies, reflecting the improved transduction process.

In patients treated in the phase 1/2 studies, the median level of gene therapy-derived Hb (HbAT87Q) remained stable over time: 6.4 g/dL at 24 months (n=22), 6.7 g/dL at 36 months (n=22), 6.6 g/dL at 48 months (n=22), and 7.1 g/dL at 60 months (n=10). Similarly, in patients treated in the phase 3 studies, median HbAT87Q was 9.5 g/dL at 24 months (n=10).

In LTF-303, 64% of patients in the phase 1/2 studies achieved and maintained TI for a median duration of 51.2 months, with a weighted average Hb of 10.4 g/dL (range, 9.4-13.3 g/dL), and 90% of patients treated in phase 3 studies achieved and maintained TI, with a median duration of 26.1 months and a weighted average Hb of 12.5 g/dL (range, 11.9-13.5 g/dL). At last follow up (median, 39.4 months), all of these patients remained transfusion independent.

The safety profile of beti-cel was acceptable, with no drug-product-related AEs reported beyond 2 years postinfusion, and on the day of infusion, all of the drug-product related AEs were Grade 1-2. A single drug product-related AE occurred in the 2 year follow up period: erythroid dysplasia that was noted at 24 months in a patient who remains transfusion dependent. After 2 years of follow up, all patients were alive.

“In summary, with up to 6 years of follow up data, beti-cel treatment has enabled durable transfusion independence in the majority of patients. Persistent vector positive hematopoietic cells and stable vector-derived adult HbAT87Q support this durable transfusion independence,” concluded Dr Kwiatkowski.

Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Read more of Hematology Advisor’s coverage of the ASH 2020 meeting by visiting the conference page.


Kwiatkowski JL, Walters MC, Hongeng S, et al. Long-term efficacy and safety of betibeglogene autotemcel gene therapy for the treatment of transfusion-dependent β-thalassemia: results in patients with up to 6 years of follow-up. Presented at: 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 153.