Leukemia patient

Photo by Bill Branson

VALENCIA, SPAIN—The adjunct T-cell therapy BPX-501 can make haploidentical hematopoietic stem cell transplant (haplo-HSCT) an “attractive option” for pediatric patients with acute leukemia, according to a presentation at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT).

Acute leukemia patients who received BPX-501 after haplo-HSCT in a phase 1/2 trial tended to have favorable outcomes.

At a median follow-up of 7 months, 16 of the 17 patients were alive and disease-free.

There were several cases of graft-versus-host disease (GVHD), but nearly all of these resolved.

Franco Locatelli, MD, PhD, of Bambino Gesù Children’s Hospital in Rome, Italy, presented these results at the EBMT meeting as abstract WP16.*

The trial, known as BP-004, was sponsored by Bellicum Pharmaceuticals, the company developing BPX-501.

About BPX-501

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.

The goal is to allow physicians to more safely perform haplo-HSCTs by giving patients BPX-501 to speed immune reconstitution and provide control over viral infections. But the technology is designed to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs.

The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. The idea is that, if a patient develops severe GVHD, he can receive an infusion with the small molecule rimiducid. And this will trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About BP-004

In late 2014, Bellicum initiated BP-004, a phase 1/2 trial in children with leukemias, lymphomas, or orphan inherited blood disorders. The trial is being conducted in European and US pediatric transplant centers and is set to enroll up to 90 patients.

At the EBMT meeting, researchers reported results in 41 patients treated on this trial.

Dr Locatelli presented data on 17 patients with acute leukemias—13 with acute lymphoblastic leukemia and 4 with acute myeloid leukemia. Their median age at HSCT was 6.5 years (range, 0.9-16.1)

All of these patients received a T-cell-depleted haplo-HSCT without post-transplant GVHD prophylaxis. All were in complete remission at the time of transplant.

The patients received BPX-501 within 14 ± 4 days after haplo-HSCT. The phase 1 portion of the trial consisted of a classical 3+3 design, with 3 cohorts receiving escalating doses of BPX-501 cells—2.5 x 10⁵, 5 x 10⁵, and 1 x 10⁶ cells/kg.

In the phase 2 portion, patients received 1 X 10⁶ BPX-501 cells/kg. Rimiducid was only used in the event of uncontrollable GVHD.

Results

The median follow-up was 7 months (range, 1-15.6). The median time to platelet recovery was 11 days (range, 9-13), and the median time to neutrophil recovery was 17 days (range, 10-22).

Three patients developed skin-only acute GVHD, were treated with topical steroids, and the GVHD resolved. Two patients developed acute grade 3 GVHD, were treated with systemic steroids, and the GVHD resolved.

Two patients developed mild chronic GVHD, received systemic steroids, and the GVHD resolved. And 1 patient developed severe chronic GVHD, received systemic steroids and rimiducid, and the GVHD improved.

One patient relapsed. The estimated 1-year disease-free survival was 92.9%. Dr Locatelli noted that, although the follow-up is still limited, these results compare favorably to results in historical controls.

“These interim results continue to be very encouraging and indicate that a haploidentical transplant, with the addition of BPX-501-modified donor T cells, can be an attractive option for children in need of a transplant,” he said.

“Future studies will address the role of repeated infusions or higher numbers of BPX-501 cells in malignant patients with resistant disease.”

The BP-004 trial also included 24 patients with nonmalignant disorders. Results in these patients were presented at the EBMT meeting as abstract O007.

*Information in the abstract differs from that presented at the meeting.

Therapy may improve haplo-HSCT in leukemia patients