While rates of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem-cell transplantation “remain unacceptably high” in many settings, GVHD rates were around 5% in patients receiving Orca-T, a high-precision, regulatory T-cell-engineered donor product, according to investigators.
Everett Meyer, MD, PhD, of Stanford University in Palo Alto, California, and colleagues conducted the study to investigate the safety and efficacy of Orca-T in patients with hematologic malignancies. Orca-T is an “allogeneic investigational cell therapy product comprised of stem and immune cells that leverages highly purified, polyclonal donor regulatory T-cells to control alloreactive immune responses,” Dr. Meyer and colleagues wrote.
Samer Srour, MB ChB, MS, of the University of Texas MD Anderson Cancer Center, gave a presentation on the research during the Tenth Annual Meeting of the Society of Hematologic Oncology (SOHO).
“Our goal is to decrease the graft-versus-host disease [incidence] significantly without increasing the relapse [rate],” Dr. Srour said during his presentation.
Dr. Srour reported on data from a single-center phase I/II study of Orca-T (n=41) and a multicenter phase Ib study (n=97) that both included patients with high-risk hematologic malignancies who received Orca-T.
The median patient age was 49 years. Most patients had acute myeloid leukemia (43%), 27% had acute lymphoblastic leukemia, 10% had myelodysplastic syndrome, 7% had myelofibrosis, and 6% had chronic myelogenous leukemia. All patients had at least 100 days of follow-up as of February 28, 2022. The median follow-up was 300 days (range, 27-1941 days).
Orca-T was produced from granulocyte colony-stimulating, factor-mobilized peripheral blood from matched related donors (n=72), matched unrelated donors (n=62), or mismatched unrelated donors (n=4).
“Orca-T was successfully manufactured, distributed, and infused for all patients,” the researchers wrote. “Overall time from donor centers to recipient centers was under 60 hours in all cases.”
Most patients received busulfan-based myeloablative conditioning (79%), while 19.5% received total body irradiation-based conditioning, and 1.5% received carmustine-based conditioning. Almost all patients (92%) received single-agent tacrolimus as GVHD prophylaxis, while 7 patients received sirolimus, and 4 patients received tacrolimus plus mycophenolate.
The median time to neutrophil engraftment was 13 days, and the “engraftment was really robust,” Dr. Srour said during his presentation at SOHO.
occurred in 4% of patients in the first 180 days, while moderate-to-severe chronic GVHD occurred in 5% of patients through the first year. The nonrelapse mortality rate was 4% through the first year. Patients receiving Orca-T had a GVHD-free relapse-free survival rate of 71%.
“We achieved excellent outcomes regarding the graft-versus-host and relapse [rates],” Dr. Srour said.
The overall survival rate was 90% at 1 year, which is “amazing in the transplant field,” Dr. Srour said. “Your patients are happy at 1 year, back to doing whatever they want to do in their life.”
Researchers are currently enrolling patients for a multicenter randomized-control phase III trial comparing Orca-T with standard-of-care therapy, he said.
“I believe this will be practice-changing in a few years. Hopefully we can get [United States Food and Drug Administration] approval if we can prove it,” he concluded.
Meyer E, Pavlova A, Gandhi A, et al. Orca-T, a precision engineered allograft, results in high GVHD-free and relapse-free survival following myeloablative conditioning for hematological malignancies. Oral abstract CT-524. Presented at the Tenth Annual Meeting of the Society of Hematologic Oncology; September 28-October 1, 2022; Houston, TX.