Administration of BPX-501 Cells Following Αβ T and B-Cell-Depleted HLA-Haploidentical HSCT (haplo-HSCT) in Children with Malignant or Non-Malignant Disorders

Abstract

Background Allogeneic HSCT is an established treatment for children with leukemia or life-threatening non-malignant disorders. Approx. 25% of pts lack a suitable donor. HLA-partially matched donors represent an alternative for these pts. BPX-501 is an allogeneic product consisting of T cells modified to express the inducible caspase-9 (iC9) safety switch and truncated CD19 to allow monitoring and expansion of CD3 + CD19 + T-cells following transplant. BPX-501 T cells provide broad virus and tumor-specific immunity; the safety switch provides the unique ability to promptly and durably resolve graft-versus-host disease (GvHD) symptoms following the administration of rimiducid. Aims Evaluate the safety and efficacy of BPX-501 in pediatric pts with malignant or non-malignant disorders. Primary endpoint is event-free survival (EFS) at 180 days [events include transplant related mortality (TRM) (or NRM [non-relapse related mortality] for malignant patients), severe GVHD (acute Grade 2-4 organ or extensive chronic GVHD) and life-threatening infections]. Methods This multicenter EU (NCT02065869), prospective trial utilizes αβ-T and B-cell-depleted haplo-HSCT followed by infusion of donor lymphocytes with iC9. BPX-501 was planned to be infused on day14±4 after the allograft with no post-transplant GvHD prophylaxis allowed. Pts developing steroid-resistant GvHD could receive ≥1 dose of rimiducid activating iC9. Results As of June 30, 2018, 166 pts (described in Table 1) were efficacy evaluable . Median time for neutrophil and platelet engraftment was 16 and 11 days, respectively. No pts experienced graft failure. Three pts (1.8%) developed Grade III-IV aGvHD. Of 132 evaluable pts, 9 (7.2%) developed cGvHD with 2 experiencing moderate – severe cGvHD. Eleven pts received rimiducid; 10 pts had at least 1 post administration response assessment. The best overall response rate (CR/PR) was 100% with 9 pts (90%) achieving CR. EFS was 92.7%. At a median f/u of 17.6 mos, 5 pts (3.3%) experienced TRM. DFS and OS were 89.4% and 94.2%, respectively. By day 100, CD3 + and CD3 + CD4 + T cells above were > 500 cells/ml were achieved by day 100. IgA and IgM levels achieved normal values by day 180. Conclusion Preliminary efficacy outcomes demonstrate a highly effective transplantation strategy for pediatric pts with malignant or non-malignant disorders. Overall rates of GvHD were low with few cases of high-grade GvHD. Rimiducid was an effective treatment for pts with steroid-refractory GvHD.