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

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.51-52
• Main Authors: Kwiatkowski, Janet L., Walters, Mark C., Hongeng, Suradej, Locatelli, Franco, Rasko, John E.J., Cavazzana, Marina, Chen, Ying, Colvin, Richard A., Thompson, Alexis A.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-135850

▪ Introduction The goal of betibeglogene autotemcel (beti-cel; LentiGlobin for β-thalassemia) gene therapy in patients with transfusion-dependent β-thalassemia (TDT) is lifelong, stable production of functional adult hemoglobin (Hb) sufficient for transfusion independence (TI) and reduction in ineffective erythropoiesis. 60 patients with TDT have been treated with beti-cel across 2 completed phase 1/2 studies (HGB-204, HGB-205) and in 2 ongoing phase 3 studies (HGB-207, HGB-212). After 2-yrs of follow-up in these 4 parent studies, patients were invited to enroll in a 13-yr long-term follow-up study, LTF-303 (NCT02633943). Interim results of patients enrolled in LTF-303 with follow-up as long as 6 years are reported. Methods Autologous CD34+ cells were transduced with BB305 lentiviral vector and infused into patients following single-agent, pharmacokinetic-adjusted busulfan myeloablation. Transduction in the phase 3 studies used a refined manufacturing process compared to the phase 1/2 studies. LTF-303 assessments include Hb, peripheral blood vector copy number (PB VCN), assessment of erythropoiesis and iron overload, quality of life, adverse events (AEs), replication-competent lentivirus (RCL), and insertion site analysis. Data are analyzed as median (min - max). Results As of 3 March 2020, all 32 patients who completed the parent studies (age at enrollment in parent study: 20 [12 - 35] yrs) enrolled in LTF-303 (22 treated in phase 1/2 studies, 10 treated in phase 3 studies). Follow-up post-infusion was 49.1 (23.3 - 71.8) months. PB VCN was detected in all patients at last follow-up (Phase 1/2: 0.4 [0.07 - 4.0] c/dg; Phase 3: 2.0 [0.13 - 3.0] c/dg). Gene therapy-derived Hb, HbAT87Q,in patients treated in the phase 1/2 studies was stable over time: 6.4 (0.5 - 10.1), 6.7 (0.4 - 10.1), 6.6 (0.5 - 10.7), and 7.1 (2.8 - 11.2) g/dL at months 24 (n=22), 36 (n=22), 48 (n=22), and 60 (n=10). Median HbAT87Q at month 24 in patients treated in the phase 3 studies was 9.5 (0.9 - 12.4) g/dL (n=10). Of the 32 patients enrolled in LTF-303, TI (defined as a weighted average Hb ≥9 g/dL without packed red blood cell transfusions for ≥12 months) was achieved in 14/22 (64%) patients treated in phase 1/2 (12 achieved TI during parent study, 2 during LTF-303) and in 9/10 (90%) patients treated in phase 3 (all achieved TI in parent study). All patients remain TI at last follow-up for 39.4 (19.4 - 69.4) months. Weighted average Hb during TI was 10.4 (9.4 - 13.3) and 12.5 (11.9 - 1