Contributions
Abstract: S128
Type: Oral Presentation
Presentation during EHA22: On Friday, June 23, 2017 from 11:30 - 11:45
Location: Room N105
Background
Gene therapy for transfusion dependent beta-thalassemia, as an alternative cure to allogeneic HSCT, is based on the autologous transplantation of hematopoietic stem cells (HSCs) engineered by lentiviral vectors expressing a transcriptionally regulated human beta-globin gene.
Aims
Our contribution to this field was devoted to the clinical development of a gene therapy protocol based on high-titer vector GLOBE, use of lenograstim and plerixafor as source of HSCs and a conditioning regimen based on myeloablative treosulfan and thiotepa favoring efficient engraftment of corrected cells with reduced toxicity (TIGET-BTHAL; EudraCT number 2014‐004860‐39).
Methods
On the basis of extensive efficacy and safety preclinical studies the clinical trial TIGET-BTHAL was approved and started in 2015 at Scientific Institute San Raffaele, Milan, Italy. The clinical study foresees treatment of 10 patients: 3 adults followed by 7 minors, with a staggered enrolment strategy based on evaluation of safety and preliminary efficacy in adult patients by an independent data safety monitoring board before inclusion of pediatric subjects. The chosen route of administration of gene modified HSCs is intraosseous in the posterior-superior iliac crests, bilaterally, with the aim of enhancing engraftment and minimizing first-pass intravenous filter.
Results
As of February 2017, seven patients (3 adults and 4 pediatric patients) with different genotypes (β0/β0, β+/β+ and β0/β+) have been treated with GLOBE-transduced CD34+ cells at a dose of 16x106-19.5x106 cells/kg and a vector copy number (VCN)/cell ranging from 0.7 to 1.5. The procedure was well tolerated by all patients, with no product-related adverse events. Multilineage engraftment of gene-marked cells was observed in all tested peripheral blood and bone marrow samples. Polyclonal vector integrations profiles have been detected in the first 3 patients tested.
Conclusion
So far, the clinical outcome indicates reduction in transfusion requirement in adult patients and greater clinical benefit in younger patients. Follow up analysis are ongoing and updated clinical outcome will be presented.
Session topic: 26. Thalassemias
Keyword(s): Thalassemia, Gene therapy, Autologous peripheral blood stem cell tansplantati
Abstract: S128
Type: Oral Presentation
Presentation during EHA22: On Friday, June 23, 2017 from 11:30 - 11:45
Location: Room N105
Background
Gene therapy for transfusion dependent beta-thalassemia, as an alternative cure to allogeneic HSCT, is based on the autologous transplantation of hematopoietic stem cells (HSCs) engineered by lentiviral vectors expressing a transcriptionally regulated human beta-globin gene.
Aims
Our contribution to this field was devoted to the clinical development of a gene therapy protocol based on high-titer vector GLOBE, use of lenograstim and plerixafor as source of HSCs and a conditioning regimen based on myeloablative treosulfan and thiotepa favoring efficient engraftment of corrected cells with reduced toxicity (TIGET-BTHAL; EudraCT number 2014‐004860‐39).
Methods
On the basis of extensive efficacy and safety preclinical studies the clinical trial TIGET-BTHAL was approved and started in 2015 at Scientific Institute San Raffaele, Milan, Italy. The clinical study foresees treatment of 10 patients: 3 adults followed by 7 minors, with a staggered enrolment strategy based on evaluation of safety and preliminary efficacy in adult patients by an independent data safety monitoring board before inclusion of pediatric subjects. The chosen route of administration of gene modified HSCs is intraosseous in the posterior-superior iliac crests, bilaterally, with the aim of enhancing engraftment and minimizing first-pass intravenous filter.
Results
As of February 2017, seven patients (3 adults and 4 pediatric patients) with different genotypes (β0/β0, β+/β+ and β0/β+) have been treated with GLOBE-transduced CD34+ cells at a dose of 16x106-19.5x106 cells/kg and a vector copy number (VCN)/cell ranging from 0.7 to 1.5. The procedure was well tolerated by all patients, with no product-related adverse events. Multilineage engraftment of gene-marked cells was observed in all tested peripheral blood and bone marrow samples. Polyclonal vector integrations profiles have been detected in the first 3 patients tested.
Conclusion
So far, the clinical outcome indicates reduction in transfusion requirement in adult patients and greater clinical benefit in younger patients. Follow up analysis are ongoing and updated clinical outcome will be presented.
Session topic: 26. Thalassemias
Keyword(s): Thalassemia, Gene therapy, Autologous peripheral blood stem cell tansplantati