Infusion of BPX-501 T Cells Renders Haplo-HSCT a First-Line Option for Children with PI

Results from a Phase I/II study indicate that haploidentical hematopoietic stem cell transplantation (haplo-HSCT), after depletion of α/β T cells and B cells followed by adoptive infusion of donor BPX-501 cells, is an effective alternative for children with primary immunodeficiency disease (PI) in need of an urgent allograft or lacking a suitable human leukocyte antigen (HLA)-matched donor. While haplo-HSCT after depletion of α/β T cells/CD19 B cells previously had high success rates, many patients had a delay in recovery of adaptive immunity, sometimes resulting in life-threatening or even fatal events. BPX-501 cells expand in vivo and persist over time, contributing to hasten the recovery of adaptive T-cell immunity and to clear infections.

In the multicenter, prospective trial, 20 children with PIs were enrolled. All patients were transplanted after depletion of α/β T cells and CD19 B cells, employed to prevent graft-versus-host disease (GvHD) and post-transplant lymphoproliferative disorders. No patient was given any post-transplantation GvHD prophylaxis. Four patients were enrolled in the Phase I portion of the trial, which consisted of a classical 3+3 design with three cohorts, with escalating doses of BPX-501 cells of 2.5×105 (one patient), 5×105 (no patients) and 1×106 cells/kg (three patients), respectively. The remaining 16 patients were treated in the Phase II portion, all of whom received the highest dose identified during the Phase I portion (1×106 cells/kg). All patients engrafted, and no secondary graft failure was recorded. The median time to neutrophil and platelet recovery was 16 days (range 11- 35) and 10 days (range 7-14), respectively. BPX-501 cells were infused at a median time of 15 days (range 13-56) after the allograft. Five children experienced grade I (three patients) or grade II (two patients) acute GvHD, which resolved with either topical or systemic steroids in three patients. The other two cases resolved after the infusion of Rimiducid, which activated the iC9 suicide gene. Two of the patients at risk developed mild (skin-only) chronic GvHD. The median time to discharge was 36 days, with eight patients experiencing one episode of rehospitalization after initial discharge. After a median follow-up of 10 months, all patients are alive and disease-free.