Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) constitutes a curative treatment for children with malignant and non-malignant disorders. HLA-partially matched haploidentical (haplo) donors represent a viable alternative option for those children who lack an HLA-compatible donor. T-cell depletion approaches with positive (CD34 selection) or negative selection (alpha/beta T-cell and CD19+ B-cell-depletion) may allow engraftment of donor cells with a low risk of GvHD; however, success is limited by delayed immune recovery, increasing the risk of fatal infections. Infusion of unmanipulated donor T cells (DLI) to accelerate immune recovery is associated with high risk of fatal GVHD. In contrast, adoptive transfer of donor T cells genetically manipulated to include a safety switch can be a suitable strategy to render DLI safer and more widely applicable.

BPX-501 is an allogeneic product consisting of T cells modified to express the inducible caspase-9 (iC9) safety switch. The polyclonal natural of these modified T cells can provide viral immunity following stem cell transplant, with the unique ability to promptly and durably resolve GvHD symptoms following the administration of rimiducid, an inert, lipid-permeable compound that rapidly induces dimerization and activation of iC9, inducing apoptosis of the gene modified T cells.


To evaluate the safety and efficacy of rimiducid in the treatment of GvHD following administration of BPX-501 T cells in pediatric patients with malignant or non-malignant disorders given an αβ T-cell receptor and B-cell depleted haplo-HSCT. A key objective of this study is to assess the activity of rimiducid infusion following onset of GvHD which is refractory to standard of care therapies.


Two multicenter (US [NCT03301168] and EU [NCT02065869]), prospective trials utilized αβ-T-cell and B-cell-depleted haplo-HSCT followed by infusion of a titrated number of donor lymphocytes genetically modified with iC9 (BPX-501 T cells) in patients with malignant or non-malignant disorders. BPX-501 T-cells were planned to be infused on day14+/-4 after the allograft. No post-transplant pharmacological GvHD prophylaxis was employed. Patients who develop GvHD resistant to conventional steroid therapy could receive ≥1 dose of dimerizing rimiducid to activate the iC9 safety gene.

The efficacy evaluable population is defined as any patient who received ≥ 1 dose of rimiducid for the treatment of GvHD and had a follow up response assessment.


At the time of clinical cut-off (June 30th, 2018) 249 patients with a malignant (41.4%) or non-malignant disorder (58.6%) were enrolled. The conditioning regimens varied according to the original disease and were Treosulfan-based (14.9%), Busulfan-based (28.9%), TBI-based (34.9%) or other (19.3%). The donor was a parent in 229 children (92 %), a sibling in 17 (6.8 %), and a half-sibling in the remaining 3 (1.2 %). The median time to BPX-501 infusion was 18 days (10 - 66 days).

Fifty-two patients developed Grade I-IV aGvHD (cumulative incidence [CI] 21.9 % [95% confidence interval (CoI): 16.7 - 27.2]). Twenty-six patients developed Grade II-IV aGvHD (CI 10.9 %). Five patients developed Grade III-IV aGvHD (CI 2.1 %). Eight patients developed cGvHD (CI of 4.6% [95% CoI: 1.3 - 7.8]).

Twenty-one patients met the rimiducid efficacy evaluable population definition. An overall clinical response rate of 86% was observed. A CR or PR to rimiducid was observed in 12 and 6 patients, respectively. Median time to initial response was 2 days (1-61 days). Median number of doses received was 1 (1 - 2). At a median follow-up of 7.8 months (2.3 - 30.8 months), 77% of the initial responders were still in either complete (n=8) or partial response (n=6).


These data suggest that administration of rimiducid for treatment of steroid-refractory GvHD represents a novel and highly effective treatment approach in pediatric patients with non-malignant or malignant disorders who received a αβ-T-cell and B-cell depleted haplo-HSCT followed by infusion of BPX-501 cells. The administration of rimiducid in children given BPX-501 T cells allows for effective control of GvHD occurring after the adoptive transfer of genetically modified T cells.


Slatter:Medac: Other: Travel assistance. Merli:Neovii Biotech: Honoraria; AMGEN: Honoraria. Aldinger:Bellicum Pharmaceuticals, Inc.: Employment. Locatelli:Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy.

Author notes


Asterisk with author names denotes non-ASH members.

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