Contributions
Abstract: S871
Type: Oral Presentation
Presentation during EHA23: On Saturday, June 16, 2018 from 16:00 - 16:15
Location: Room A6
Background
Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is a well-established treatment for children with a wide range of primary immunodeficiencies (PIDs). HLA partially-matched (haplo) donors are a suitable alternative option for children who lack a matched donor.
Aims
To evaluate the safety and efficacy of BPX-501 T cells administered after a T-cell receptor αβ and B-cell depleted haplo-HSCT in pediatric patients with PIDs. The purpose of this clinical trial is to determine whether BPX-501 infusion can enhance immune reconstitution and reduce the risk of life-threatening infections.
Methods
Fifty-nine (59) patients (EU:42, US:17; 34 males, 25 females; median age 4.6 years) with PIDs were enrolled in a multicenter, prospective trial utilizing αβ-T-cell and B-cell-depleted haplo-HSCT, followed by infusion of donor lymphocytes genetically modified to include the inducible Casp9 suicide gene (iCasp9; BPX-501 T cells). The study included, SCID: 19 patients, WAS: 9 patients, CGD: 7 patients, HLH: 6 patients, CID: 4 patients, and other immune deficiencies: 14 patients. In the EU, the conditioning regimen was primarily-treosulfan-based (used in 47.5% of all patients), whereas in the US conditioning was most frequently busulfan-based (used in 39% of all patients). All patients received rabbit anti-thymocyte globulin (Grafalon/Neovii® or Thymoglobulin/Sanofi® in the EU and US, respectively) as graft rejection prophylaxis. Patients received 0.25-1 x 106 BPX-501 cells/kg. The median time to BPX-501 infusion was 15 days (11.00 - 56.00).
Results
The median time for neutrophil and platelet engraftment was 16 and 11 days, respectively. Six children (10.1%) experienced primary graft failure (3 HLH, 1 CID, 2 CGD). Five patients engrafted after a successful second transplant (4 haplo, 1 unrelated cord blood). Twenty patients developed Grade I-IV aGVHD (cumulative incidence [CI] 35.1% [95% confidence interval (CoI): 22.6-47.6]). Ten patients developed Grade II-IV aGVHD (CI 17.0% [95% CoI: 7.4-26.6]). Three patients developed Grade III-IV aGVHD (CI 5.5% [95% CoI: 0-11.6]). Two patients developed mild to severe cGVHD (CI of 5.1% [95% CoI: 0-12.2]). The dimerizing agent AP1903 activating iCasp9 was administered in 6 patients (2 CRs, 2 PRs, 1 NE, 1 NR). Three of the 59 patients experienced transplant-related mortality (TRM CI 5.9%; 95% CoI 0-12.4%). Disease-free survival (DFS) was 88.1% (95% CI, 79.9-96.3%) after a median follow-up of 487 days (32-1147 days). The probability of overall survival was 88.6%. CD3+ and CD3+CD4+ T cells above 500 cells/ml were achieved by 90 and 180 days, respectively. IgA and IgM levels achieved normal values by 270 and 180 days, respectively. CD3+CD19+ cell counts above 100 cells/ml were achieved by day 90.
Conclusion
These data suggest that αβ-T-cell and B-cell depleted haplo-HSCT followed by infusion of BPX-501 cells represents a novel and highly effective transplantation strategy for many different PIDs, leading to a success rate comparable to that of matched-donor HSCT.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Allogeneic stem cell transplant, Cellular therapy, Haploidentical stem cell transplantation, Immune deficiency
Abstract: S871
Type: Oral Presentation
Presentation during EHA23: On Saturday, June 16, 2018 from 16:00 - 16:15
Location: Room A6
Background
Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is a well-established treatment for children with a wide range of primary immunodeficiencies (PIDs). HLA partially-matched (haplo) donors are a suitable alternative option for children who lack a matched donor.
Aims
To evaluate the safety and efficacy of BPX-501 T cells administered after a T-cell receptor αβ and B-cell depleted haplo-HSCT in pediatric patients with PIDs. The purpose of this clinical trial is to determine whether BPX-501 infusion can enhance immune reconstitution and reduce the risk of life-threatening infections.
Methods
Fifty-nine (59) patients (EU:42, US:17; 34 males, 25 females; median age 4.6 years) with PIDs were enrolled in a multicenter, prospective trial utilizing αβ-T-cell and B-cell-depleted haplo-HSCT, followed by infusion of donor lymphocytes genetically modified to include the inducible Casp9 suicide gene (iCasp9; BPX-501 T cells). The study included, SCID: 19 patients, WAS: 9 patients, CGD: 7 patients, HLH: 6 patients, CID: 4 patients, and other immune deficiencies: 14 patients. In the EU, the conditioning regimen was primarily-treosulfan-based (used in 47.5% of all patients), whereas in the US conditioning was most frequently busulfan-based (used in 39% of all patients). All patients received rabbit anti-thymocyte globulin (Grafalon/Neovii® or Thymoglobulin/Sanofi® in the EU and US, respectively) as graft rejection prophylaxis. Patients received 0.25-1 x 106 BPX-501 cells/kg. The median time to BPX-501 infusion was 15 days (11.00 - 56.00).
Results
The median time for neutrophil and platelet engraftment was 16 and 11 days, respectively. Six children (10.1%) experienced primary graft failure (3 HLH, 1 CID, 2 CGD). Five patients engrafted after a successful second transplant (4 haplo, 1 unrelated cord blood). Twenty patients developed Grade I-IV aGVHD (cumulative incidence [CI] 35.1% [95% confidence interval (CoI): 22.6-47.6]). Ten patients developed Grade II-IV aGVHD (CI 17.0% [95% CoI: 7.4-26.6]). Three patients developed Grade III-IV aGVHD (CI 5.5% [95% CoI: 0-11.6]). Two patients developed mild to severe cGVHD (CI of 5.1% [95% CoI: 0-12.2]). The dimerizing agent AP1903 activating iCasp9 was administered in 6 patients (2 CRs, 2 PRs, 1 NE, 1 NR). Three of the 59 patients experienced transplant-related mortality (TRM CI 5.9%; 95% CoI 0-12.4%). Disease-free survival (DFS) was 88.1% (95% CI, 79.9-96.3%) after a median follow-up of 487 days (32-1147 days). The probability of overall survival was 88.6%. CD3+ and CD3+CD4+ T cells above 500 cells/ml were achieved by 90 and 180 days, respectively. IgA and IgM levels achieved normal values by 270 and 180 days, respectively. CD3+CD19+ cell counts above 100 cells/ml were achieved by day 90.
Conclusion
These data suggest that αβ-T-cell and B-cell depleted haplo-HSCT followed by infusion of BPX-501 cells represents a novel and highly effective transplantation strategy for many different PIDs, leading to a success rate comparable to that of matched-donor HSCT.
Session topic: 23. Stem cell transplantation - Clinical
Keyword(s): Allogeneic stem cell transplant, Cellular therapy, Haploidentical stem cell transplantation, Immune deficiency