Gene Therapy in Patients with Transfusion-Dependent Beta-Thalassemia

Gene Therapy in Patients with Transfusion-Dependent Beta-Thalassemia
This study evaluates the safety and efficacy of a lentiviral beta-globin gene therapy compared to long-term red-cell transfusions in patients with beta-thalassemia. This study reports interim results from two companion phase I and II clinical studies, specifically evaluating the LentiGlobin BB305 vector using a multi-center, non-randomized, open-label single-dose approach.
Patients between the ages of 5 and 35 years with any genotype of transfusion-dependent B-thalassemia were eligible. Patients had hematopoietic stem cells harvested by apheresis. CD34+ cells were transduced with BB305. Conditioning occurred with myeloablative IV busulfan followed by infusion of the LentiGlobin vector-manipulated stem cells.
22 patients were treated on the study. Treatment with the BB305 vector-manipulated stem cells reduced or eliminated the need for transfusion therapy in all 22 patients. In patients 12/13 patients with a non-β0/β0 genotype and 3/9 with a β0/β0 genotype became transfusion-independent. In those who continued to require transfusions, transfusion volume was decreased by 73%. There were no major adverse events, apart from those typically associated with autologous stem cell transplantation.
Small study in 22 patients. The treatment requires autologous stem cell transplantation and a specific lentiviral product that is not yet widely available. Safety has not yet been fully evaluated as long-term or rare side effects can not be determined from only 22 patients.
This study presents an exciting alternative to allogenic hematopoietic stem cell transplantation in patients with transfusion-dependent beta-thalassemia. Further research is required to better characterize the safety profile.