Samer A. Srour

Samer A. Srour, MD, ChB, MS
Department of Stem Cell Transplantation and Cellular Therapy
Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center

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.