Gene therapy confers durable benefits for patients with beta-thalassemia
Click Here to Manage Email Alerts
NEW ORLEANS — One-time treatment with the gene therapy betibeglogene autotemcel continued to demonstrate long-term efficacy among patients with transfusion-dependent beta-thalassemia, study results showed.
More than 90% of those who received the therapy in phase 3 studies remained free from the need for red blood cell transfusions through up to 8 years of follow-up, according to an analysis presented at ASH Annual Meeting and Exposition.
“Betibeglogene autotemcel is a potentially curative gene therapy for patients with transfusion-dependent beta-thalassemia across all ages and genotypes through the achievement of transfusion independence and normal or near-normal hemoglobin levels,” Franco Locatelli, MD, PhD, head of the department of pediatric hematology and oncology at IRCCS Bambino Gesù Children’s Hospital in Rome,” said during a press conference.
Background
Betibeglogene autotemcel (Zynteglo, bluebird bio), also known as beti-cel, is a one-time ex vivo gene therapy that adds functional copies of a modified form of the beta-globin gene into a patient’s hematopoietic stem cells. The FDA approved the therapy for commercial use in August for patients with beta-thalassemia who require routine red blood cell transfusions.
Patients with beta-thalassemia require regular life-sustaining transfusions plus iron chelation therapy to prevent damage due to accumulation of iron within the body’s organs.
“Despite the optimization of transfusion and the development of oral iron chelating drugs, patients with beta-thalassemia are exposed to long-term risk [for] complications,” Locatelli said. “There is a desperate need for a potentially curative treatment.”
Before the development of beti-cel, the only available curative therapy was allogeneic hematopoietic stem cell transplantation, which was limited to only those patients who an HLA-matched sibling donor, Locatelli noted.
Methodology
Locatelli and colleagues reported 8-year follow-up results and patient-reported outcomes of 63 patients who received beti-cel across four studies and enrolled in LTF-303, a 13-year follow-up study to examine the safety and efficacy of the one-time gene therapy.
Transfusion independence, defined as the weighted average of hemoglobin 9 g/dL or greater without the need for a red blood cell transfusion in the past 12 months or longer, served as the study’s primary efficacy outcome.
Median follow-up across the four parent studies plus the LTF-303 trial was 52 months (range, 20.1-101.7) with a data cutoff of July.
Key findings
Results demonstrated a 90.2% transfusion-independence rate among patients who received beti-cel as part of phase 3 trials.
Twelve of 63 patients (19%) experienced at least one adverse event related to or possibly related to treatment with beti-cel. These included five patients (8%) with abdominal pain and three patients (5%) with thrombocytopenia.
Investigators reported veno-occlusive liver disease in seven patients (11%) that resolved after treatment.
No treatment-related malignancies, insertional oncogenesis, vector-derived replication competent lentivirus or clonal predominance occurred among these patients.
Patient-reported outcomes based on an array of quality-of-life questionnaires showed marked improvement in symptoms after treatment with beti-cel among those in the long-term study, Locatelli noted.
A 36-month outcomes assessment of patients who achieved transfusion independence after beti-cel infusion showed:
- 100% of patients reported an overall treatment benefit;
- 45% of patients no longer required management of their disease symptoms;
- 93% of patients were employed or able to look for employment compared with 67% before treatment;
- 50% of patients reported absence from school compared with 95% before treatment; and
- 81% of patients reported improvement in physical activity.
Clinical implications
“Patients with transfusion-dependent beta-thalassemia experienced durable transfusion independence up to 8 years after beti-cel infusion, which was associated with a favorable risk-benefit profile consistent with that of myeloablative autologous transplantation,” Locatelli said. “The updated data from the long-term study of patients with transfusion-dependent beta-thalassemia treated with beti-cel demonstrates quality-of-life improvement despite relatively high baseline scores.”
References:
Locatelli F, et al. Abstract 3665. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.
Walters MC, et al. Abstract 2348. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.
Collapse
Walters MC, et al. Abstract 2348. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.
Read more about
Click Here to Manage Email Alerts