-Author name in bold denotes the presenting author
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166 Administration of BPX-501 Following Αβ-T and B-Cell Depleted Haplo-HSCT in Children with Transfusion-Dependent ThalassemiaClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 112. Thalassemia and Globin Gene Regulation: Clinical
Hematology Disease Topics & Pathways:
Biological, Diseases, Therapies, Bleeding and clotting, thalassemia, Pediatric, Hemoglobinopathies, Study Population, transplantation
Saturday, December 1, 2018: 2:45 PM
Room 30D (San Diego Convention Center)

Federica Galaverna, MD1*, Daria Pagliara, MD, PhD2*, Deepa Manwani, MD3,4, Rajni Agarwal, MD5, Melissa Kuhn, PharmD6 and Franco Locatelli7

1Department of Hematology/Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
2Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
3Children's Hospital at Montefiore, Bronx, NY
4Albert Einstein College of Medicine, Bronx
5Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University Medical Center, Stanford, CA
6Bellicum Pharmaceutical, Inc., Brisbane, CA
7Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesu, Rome, Italy


Allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-identical sibling has been shown to cure most children with transfusion-dependent b-thalassemia major. Results obtained using an HLA-partially matched (haploidentical, haplo) donor have been historically less satisfactory, the thalassemia-free-survival (TFS) probability being ~ 60%. αβ T and B-cell depleted haplo-HSCT has been proposed as a novel strategy able to minimize the risk of graft-versus-host disease (GvHD) and to protect patients from the risk of life-threatening viral/fungal infections. However, recovery of adaptive immunity after this type of allograft is still suboptimal.

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 BPX-501 following transplant. The polyclonal nature of the BPX-501 provides broad virus and tumor-specific immunity, while the safety switch provides the unique ability to promptly and durably resolve graft-versus-host disease (GvHD) symptoms following the administration of rimiducid which induces dimerization and activation of iC9, inducing apoptosis of BPX-501.


To evaluate the safety and efficacy (immune recovery and risk of acute and chronic GvHD) of BPX-501 administered after a αβ T and B-cell depleted haplo-HSCT in pediatric patients with b-thalassemia.


This is a multicenter US (NCT03301168) and EU (NCT020658), prospective trial utilizing αβ-T and B-cell-depleted haplo-HSCT followed by infusion of donor lymphocytes genetically modified with iC9 (BPX-501) in patients with malignant or non-malignant disorders. A subset of patients enrolled had b-thalassemia. BPX-501 was 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 can receive ≥1 dose of dimerizing rimiducid activating iC9.

The efficacy-evaluable population (EEP) was defined as any patient with b-thalassemia who received HSCT, BPX-501 infusion and had at least one follow-up assessment.


At the time of clinical cut-off (June 30, 2018) 24 patients (EU [n=22] US [n=2]; Male [n=14] Female [n= 10]; median age 9.16 yrs (2.15 – 14.34 yrs) met the EEP definition. The median follow-up was 11.3 mos (0.5-37.4 mos).

The majority (83.3%) of patients received a busulfan-based conditioning regimen. The median HSCT CD34+ and ab TCR+ cell doses were 20.5 x 106 /kg and 0.15 x 105 /kg, respectively. The donor was a parent in all children (100%).The median time to BPX-501 infusion was 17 days (10– 36 days).

Two children experienced primary graft failure (8.7% [95% CI: 0-20.3]). One patient underwent a second HSCT with successful engraftment and remains disease free with a median follow up of 31 months. In patients who obtained sustained engraftment of donor cells, the median time for neutrophil and platelet engraftment was 15 (15 – 18) and 12 (11 – 13) days, respectively. Of 22 evaluable patients 3 patients (Grade 1 [n=1] and Grade 2 [n= 2]) developed Grade 1-II aGvHD (13.6% [95% CI: 0 – 28). No patients developed Grade III-IV aGvHD or chronic GvHD. The dimerizing agent rimiducid was administered in one patient with Grade 2 Skin aGvHD who subsequently achieved a complete response.

Two of the twenty-four patients died after transplantation from infections (9.3% [95% CI: 0 - 21.6%]). Disease-free survival (DFS) was 82.2% (95% CI: 66.3 - 98%). Overall Survival (OS) was 90.7% (95% CI: 78.4 – 100). The median time from last red blood cell transfusion was 11.1 mos (1 day – 37.2 mos).

CD3+ and CD3+CD4+ T cells above 500 cells/ml were achieved by 180 and 270 days, respectively. IgA and IgM levels achieved normal values by 30 and 180 days, respectively. The percentage of circulating and median absolute BPX-501 at Day 100 were 2.53% ± 2.62% (0 - 7.6%) and 23.94 ± 28.58 cells/ml (0 - 76.5 cells/ml), respectively.


An αβ-T and B-cell depleted haplo-HSCT followed by infusion of BPX-501 is a suitable and effective option for children with transfusion-dependent b-thalassemia major lacking an HLA-identical donor. The low cumulative incidence of TRM and the absence of severe aGvHD or chronic GvHD observed support further study in this patient population.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH