In patients with hematologic malignancies, the use of Orca-T, a high-precision cell therapy, led to a reduction in the occurrence of acute and chronic graft-versus-host disease (GVHD), while avoiding relapse after myeloablative conditioning.
Samer A. Srour, MD, ChB, MS, and colleagues conducted an analysis of two Orca-T studies, which they presented at the 2022 Society of Hematologic Oncology (SOHO) annual meeting. Results from patients treated with Orca-T suggest a reduction in chronic GVHD, improved GVHD-free relapse-free survival, and low toxicity relative to historic data, noted Dr. Srour and team.
Moderate-to-Severe Chronic GVHD in Only 5%
Treatment with Orca-T, Dr. Srour explained, consists of conventional T cells (Tcons) and CD34+ stem cells derived from peripheral blood infusions from either unrelated or related matched donors, as well as infusions containing regulatory T cells (Tregs). “If we harmonize this graft better with Tregs, which can really decrease GVHD, and then add back some Tcons later on to preserve the graft-versus-leukemia effect without increasing significant GVHD, then you can get great outcomes,” said Dr. Srour.
The investigation included 137 patients with hematologic malignancies from a phase 2/3 study and a multicenter phase 1b study who received transplant with Orca-T and were compared with 375 patients from the Center for International Blood and Marrow Transplant Research (CIBMTR)-based control arm. Most patients had acute myeloid leukemia, myelodysplastic syndromes, or acute lymphocytic leukemia.
Only 5% of patients who underwent transplant with Orca-T developed moderate-to-severe chronic GVHD at 1 year, compared with 38% of patients in the CIBMTR arm who had a standard of care allogeneic hematopoietic stem cell transplant (alloHSCT), Dr. Srour observed.
1-Year Overall Survival Rate of 90%
Compared with 35% in the CIBMTR group, the risk for relapse was lower in the Orca-T group, at 20%. Additionally, 16% in the CIBMTR comparator arm experienced severe acute GVHD (≥ grade 3) compared with just 4% in the Orca-T arm. The GVHD- and relapse-free survival rates were 71% and 21%, respectively.
Compared with 68% in the CIBMTR arm, the overall survival rate for patients who received Orca-T was 90% at 1 year. Severe infection in the year after treatment was observed in only 10% of patients in the Orca-T arm. At medians of 13 and 16 days, neutrophil and platelet engraftment occurred in the Orca-T arm. Of the 137 patients treated with Orca-T, two graft failure events were reported.
Based on these data, Dr. Srour and colleagues predict that the [use of Orca-T cell therapy] will soon be practice-changing. In addition, a phase 3 trial evaluating Orca-T plus single-agent tacrolimus versus an unmanipulated allograft plus tacrolimus/methotrexate is currently underway and accepting patients, according to the study team.