Durable benefits with beti-cel therapy in beta-thalassaemia

One-time ex-vivo gene therapy with betibeglogene autotemcel (beti-cel) reduces the need for transfusion in patients with transfusion-dependent beta-thalassaemia in an analysis of studies presented at ASH 2022.

The treatment works by inserting functional copies of the beta-globin gene into the patient’s hematopoietic stem cells via replication-defective lentivirus to help the body produce functional adult haemoglobin, potentially eliminating the need for regular transfusions.

Nearly 90 percent of patients who received beti-cell in the studies were transfusion-free for up to 8 years post-treatment. [ASH 2022, abstract 2348]

“Betibeglogene autotemcel is a potentially curative gene therapy for patients with transfusion-dependent beta-thalassaemia across all ages and genotypes through the achievement of transfusion independence and normal or near-normal haemoglobin levels,” said study author Dr Franco Locatelli,  head of the department of paediatric haematology and oncology at IRCCS Bambino Gesù Children’s Hospital in Rome, during a press conference.

Beti-cel is US-FDA approved for children and adults with transfusion-dependent beta-thalassaemia, an inherited blood disorder in which the body does not make as much beta-globin as it should.  Patients require routine transfusions plus iron chelation to remove excess iron from the blood that can build up because of regular transfusions. 

“Despite optimal transfusion and the advent of oral iron chelating drugs, patients with beta-thalassaemia are exposed to long-term risk of complications,” Locatelli noted. “Hence, there is a desperate need for a potentially curative treatment.”

Dr Mark Walters, a paediatric haematologist/oncologist from the University of California, San Francisco, California, US who presented the long-term efficacy data, said: “We now have up to 8 years of efficacy and safety data with beti-cel. Patients experience durable transfusion independence.”

Overall, 89.5 percent of patients (34/38) in phase III testing achieved the primary outcome of transfusion independence, defined as haemoglobin levels of at least 9 g/dL or greater without the need for a red blood cell transfusion for a year or longer.

The response rate was an improvement from the phase I/II testing, in which 68.2 percent of patients (15/22) became transfusion-free, said Walters. Patients who achieved transfusion independence had reductions in markers of ineffective erythropoiesis and iron overload.

“Overall, 21 out of 37 patients who restarted chelation stopped chelation at 24 months,” he shared. “Twelve patients who achieved transfusion independence resorted to phlebotomy to remove excess iron, including six who also received iron chelation.”

Eleven patients experienced at least one adverse event that was considered related or possibly related to beti-cel. These included five patients with abdominal pain and three with thrombocytopenia, but none were observed beyond 2 years post-infusion.

No treatment-related malignancies, insertional oncogenesis, vector-derived replication-competent lentivirus, or clonal predominance were reported among patients.

The researchers reported  8-year results and patient-reported outcomes of 63 patients who received beti-cel across four studies plus a 13-year long-term, follow-up study.

As for the quality of life (QoL) – surveyed at 3 years – there were continued benefits with beti-cel through 3 years post-treatment, including positive impacts on employment, school attendance, and physical activity, said Locatelli, who led the QoL study. [ASH 2022, abstract 3665]

Ninety-three percent of patients were employed or able to seek employment, up from 68.8 percent at baseline.

School absences among children were down to 44.4 percent from 83.3 percent. Half of the patients no longer needed symptom management. Eighty percent reported improvements in physical activity.

There were also improvements on various quality-of-life scales, including physical functioning and mental health.

“The updated data demonstrate the durability of QoL improvement with beti-cel through 3 years despite relatively high baseline scores,” said Locatelli.