Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a curative option for many hematologic malignancies, but it comes with significant risks, especially graft-versus-host disease (GVHD). Scientists have long aimed to balance graft-versus-tumor (GVT) and graft-versus-leukemia (GVL) effects while minimizing GVHD. Orca-T, a precision cell therapy, combines stem and immune cells, utilizing purified donor regulatory T cells to control harmful immune responses.
A study presented at the 11th Annual Meeting of the Society of Hematologic Oncology (SOHO), Houston, Texas, examined outcomes of 151 patients who received Orca-T for hematologic malignancies and had at least 100 days of follow-up. These patients were in complete remission and underwent myeloablative conditioning (MAC) followed by GVHD prophylaxis with either tacrolimus or sirolimus. Results were compared to a control group that received traditional allo-HSCT with peripheral blood stem cell (PBSC) source and tacrolimus/methotrexate prophylaxis.
The cohort who received Orca-T achieved rapid engraftment and a minimal graft failure rate (1.6%) and demonstrated significantly better outcomes at 1 year, with a 70% GVHD-free, relapse-free survival (GRFS) rate and an 88% overall survival (OS) rate compared to the control cohort’s 21% GRFS and 68% OS. In addition, non-relapse mortality (NRM) was lower with Orca-T (4%) compared to the control group (10%) at 1 year.
Patients who received a specific conditioning regimen of busulfan, fludarabine, and thiotepa with Orca-T showed exceptional outcomes, including an 87% relapse-free survival (RFS) rate and no NRM at 1 year. Severe acute GVHD and moderate-to-severe chronic GVHD rates were low, with an 81% GRFS and 94% OS at 1 year.
Orca-T demonstrated robust GVT and GVL effects while successfully reducing GVHD and non-relapse mortality, even when combined with myeloablative conditioning. These findings suggest that Orca-T can potentially enhance outcomes in allo-HSCT. A phase 3 clinical trial is currently underway to further evaluate its efficacy compared to standard treatment.
Reference
Salhotra A, Oliai C, Hoeg RT, et al. Precision-Engineered Cell Therapy Orca-T Demonstrates High Relapse-Free Survival at 1 Year While Reducing Graft-Versus-Host Disease (GvHD) and Toxicity. Abstract AML-643. Presented at the 11th Annual Meeting of the Society of Hematologic Oncology; September 6-9, 2023; Houston, Texas.
