Transplant With Orca-T Reduced GVHD in Hematologic Malignancies

Use of Orca-T, a high-precision cell therapy, led to a reduction in incidence of acute and chronic graft-versus-host disease (GVHD), while avoiding relapse following myeloablative conditioning in patients with hematologic malignancies, an analysis of two studies showed.

Compared with 38% of patients in an independent Center for International Blood and Marrow Transplant Research (CIBMTR)-based control arm who underwent standard-of-care allogeneic hematopoietic stem cell transplant (alloHSCT), only 5% of patients who received transplant with Orca-T developed moderate-to-severe chronic GVHD at 1 year, reported Samer A. Srour, MB, ChB, MS, of the University of Texas MD Anderson Cancer Center in Houston.

Moreover, risk of relapse appeared to be lower, with a rate of 20% in the Orca-T group compared with 35% in the CIBMTR group, he noted at the Society of Hematologic Oncology annual meeting.

In addition, just 4% of patients in the Orca-T arm experienced severe acute GVHD (≥ grade 3) versus 16% in the CIBMTR comparator arm, and the GVHD-free and relapse-free survival rate was 71% versus 21%, respectively.

Based on these data, “I believe this will be practice-changing in a few years,” Srour said.

The researchers also found that the overall survival rate for patients who received Orca-T was 90% at 1 year compared with 68% in the CIBMTR arm. Only 10% of patients in the Orca-T arm experienced severe infections in the year after treatment.

“The way conventional transplant is most commonly done across the world is you take the graft as it is with over 50 of the cells and you throw them in the patient,” explained Srour. “And you basically do in vivo manipulation by giving some immunosuppressive medications and try to mitigate the GVHD and try to decrease relapse.”

“In Orca-T, we thought, ‘is there any better way to do this?'” he added. “Can we clean up some of these bad cells we don’t need from the graft, and then harmonize those T cells in different ways?”

Treatment with Orca-T consists of infusions containing regulatory T cells (Tregs), as well as conventional T cells (Tcons) and CD34+ stem cells derived from peripheral blood from either related or unrelated matched donors.

In his presentation, Srour referred to the work of Robert Negrin, MD, at Stanford University, as well as others, which has shown that Tregs can prevent GVHD without increasing the risk of relapse and infection.

“If you completely deplete a graft from the T cells, you end up having relapse and poor survival, because there is no graft-versus-leukemia effect,” Srour explained. “When you add Tcons, you start getting some GVHD with some graft-versus-leukemia effect, and many patients will die from complications and graft-versus-host disease. But, 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.”

This analysis included a total of 137 patients with hematologic malignancies from a single-center phase I/II study (median age 42, 71% men) and a multicenter phase Ib study (median age 51, 52% men) who received transplant with Orca-T. They compared these patients with 375 from the CIBMTR (median age 52, 57% men). Most patients were white, and most patients had acute myeloid leukemia, acute lymphocytic leukemia, or myelodysplastic syndromes.

Neutrophil and platelet engraftment occurred at a median of 13 and 16 days in the Orca-T arm. Two graft failure events were reported in the 137 patients treated with Orca-T.

A phase III trial evaluating Orca-T plus single-agent tacrolimus versus an unmanipulated allograft plus tacrolimus/methotrexate is open and accruing, Srour noted.

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