Contributions
Abstract: S814
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:00 - 08:15
Location: Room N111
Background
Standard treatment for transfusion-dependent β-thalassemia (TDT) includes regular red blood cell (RBC) transfusions and management of iron overload. Successful allogeneic hematopoietic cell transplantation (HCT) can eliminate RBC transfusions and, eventually, chelation. However, due to transplant-related risks such as graft-versus-host disease (GVHD), as well as donor constraints, HCT is rarely an option for TDT patients. By transferring a functioning copy of the β-globin (HBB) gene into hematopoietic stem cells (CD34+ cells) and re-infusing the modified cells, gene therapy may be an alternative one-time treatment available to all patients with TDT, without risks of GVHD.
Aims
To evaluate safety and efficacy of autologous HCT with LentiGlobin DP in patients with TDT and a non-β0/β0 genotype.
Methods
After providing informed consent, patients 12 to 50 years of age (N=15) will have CD34+ cells collected via mobilization and apheresis. After individualized DP manufacture and satisfaction of release criteria, the patient will receive myeloablative conditioning with single-agent busulfan (starting dose 3.2 mg/kg/day for 4 days, with target AUC 4500 [range 4000−5000] µM*min) followed by infusion of LentiGlobin DP. Patients will be followed for engraftment, safety and efficacy endpoints for 2 years after infusion; patients will then have the option to enroll in a 13-year follow-up study. The primary endpoint is the proportion of patients who achieve transfusion independence after DP infusion, defined as total Hb ≥9g/dL without RBC transfusions for a continuous period of ≥12 months. Secondary endpoints include time to neutrophil engraftment, adverse events, and biological parameters including VCN in peripheral blood and levels of HbAT87Q over time.
Results
As of March 1, 2017, two 20-year-old females with β0/βE genotypes have been treated with LentiGlobin DP in the Northstar-2 trial. The DP VCN was 2.9 and 2.4 copies per diploid genome, respectively. Outcomes in all evaluable patients will be presented.
Conclusion
Results from the Northstar-2 study will provide data on safety and demonstrate the extent to which an increase in LentiGlobin DP VCN yields normalization of total Hb and consistently achieves transfusion independence in patients with TDT of non-β0/β0 genotypes. Optimizing DP VCN has the potential to improve outcomes across all TDT genotypes treated by investigational LentiGlobin gene therapy.
Session topic: 24. Gene therapy, cellular immunotherapy and vaccination
Keyword(s): Thalassemia, Lentiviral vector, Gene therapy
Abstract: S814
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:00 - 08:15
Location: Room N111
Background
Standard treatment for transfusion-dependent β-thalassemia (TDT) includes regular red blood cell (RBC) transfusions and management of iron overload. Successful allogeneic hematopoietic cell transplantation (HCT) can eliminate RBC transfusions and, eventually, chelation. However, due to transplant-related risks such as graft-versus-host disease (GVHD), as well as donor constraints, HCT is rarely an option for TDT patients. By transferring a functioning copy of the β-globin (HBB) gene into hematopoietic stem cells (CD34+ cells) and re-infusing the modified cells, gene therapy may be an alternative one-time treatment available to all patients with TDT, without risks of GVHD.
Aims
To evaluate safety and efficacy of autologous HCT with LentiGlobin DP in patients with TDT and a non-β0/β0 genotype.
Methods
After providing informed consent, patients 12 to 50 years of age (N=15) will have CD34+ cells collected via mobilization and apheresis. After individualized DP manufacture and satisfaction of release criteria, the patient will receive myeloablative conditioning with single-agent busulfan (starting dose 3.2 mg/kg/day for 4 days, with target AUC 4500 [range 4000−5000] µM*min) followed by infusion of LentiGlobin DP. Patients will be followed for engraftment, safety and efficacy endpoints for 2 years after infusion; patients will then have the option to enroll in a 13-year follow-up study. The primary endpoint is the proportion of patients who achieve transfusion independence after DP infusion, defined as total Hb ≥9g/dL without RBC transfusions for a continuous period of ≥12 months. Secondary endpoints include time to neutrophil engraftment, adverse events, and biological parameters including VCN in peripheral blood and levels of HbAT87Q over time.
Results
As of March 1, 2017, two 20-year-old females with β0/βE genotypes have been treated with LentiGlobin DP in the Northstar-2 trial. The DP VCN was 2.9 and 2.4 copies per diploid genome, respectively. Outcomes in all evaluable patients will be presented.
Conclusion
Results from the Northstar-2 study will provide data on safety and demonstrate the extent to which an increase in LentiGlobin DP VCN yields normalization of total Hb and consistently achieves transfusion independence in patients with TDT of non-β0/β0 genotypes. Optimizing DP VCN has the potential to improve outcomes across all TDT genotypes treated by investigational LentiGlobin gene therapy.
Session topic: 24. Gene therapy, cellular immunotherapy and vaccination
Keyword(s): Thalassemia, Lentiviral vector, Gene therapy