The use of a high-precision, allogeneic investigational cell therapy was associated with a reduction in chronic graft versus host disease (cGVHD), an improvement in GVHD-free relapse-free survival (GRFS), and less than expected toxicity relative to historic data in patients with hematologic malignancies, according to results from a single-center phase Ib/II study and a multicenter phase Ib trial. The trials were designed to evaluate the safety and efficacy of the therapy Orca-T. Everett Meyer, MD, PhD, of Stanford University in California, presented study findings at the European Hematology Association (EHA) 2022 Congress.
Patients who receive a myeloablative allogeneic hematopoietic cell transplant (alloHCT) suffer from high rates of GVHD and non-relapse mortality. Orca-T, a cell therapy composed of donor cells designed to holistically improve outcomes in these patients, leverages highly purified, polyclonal donor regulatory cells to create a combination hematopoietic and immune cell product that reduces the need for pharmacologic GVHD prophylaxis.
As of February 28, 2022, 138 patients with high-risk hematologic malignancies received Orca-T and more than 100 days of follow-up. The therapy was prepared from granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood from matched related donors (n=72), matched unrelated donors (n=62), or mismatched unrelated donors (n=4). The median follow-up for recipients was 300 days (range = 27-1,941). Patients received myeloablative conditioning followed by GVHD prophylaxis with either single-agent tacrolimus, sirolimus, or tacrolimus with mycophenolate.
In the first 180 days, 4% of patients in the therapy group exhibited grade ≥3 acute GVHD compared with 16% of patients in the control arm. Through one year, the rate of moderate to severe cGVHD was 5% in the therapy group compared to 38% in the control group. Non-relapse mortality through one year was 4% in the therapy group compared to 10% in the control group. At one year, the rates of GRFS and overall survival (OS) were 71% and 90% in the therapy group, respectively, compared to 34% and 68%, respectively, in the control group.
Additional results from a study presented at the 2022 Tandem Meetings of the American Society for Transplantation and Cellular Therapy and Center for International Blood and Marrow Transplant Research (CIBMTR) showed the therapy was superior to myeloablative alloHCT for measures of moderate-to-severe cGVHD, GRFS, and OS. Investigators used a non-randomized contextual CIBMTR comparator to determine this.
“The data continue to show the potential of Orca-T to maximize the graft-vs-leukemia effect while minimizing GVHD,” Dr. Meyer said. “For decades, the transplant community has been looking to improve OS while reducing complications such as GVHD.”
The next step, Dr. Meyer noted, will be to investigate the therapy in a phase III, registration, multicenter, randomized trial to compare it to myeloablative alloHCT for improving GVHD survival.
Any conflicts of interest by the authors were made public at the time of presentation.
Reference
Meyer E, Pavlova A, Gandhi A, et al. ORCA-T, an engineered allograft, results in high GVHD-free and relapse-free survival following myeloablative conditioning for hematological malignancies. Abstract S237. Presented at the European Hematology Association (EHA) 2022 Congress, June 12, 2022; Vienna, Austria.