ASH 2023 | Optimizing myeloablative conditioning with precision-engineered Orca-T in older patients
Caspian Oliai, MD, MS, University of California, Los Angeles, Los Angeles, CA, discusses Orca-T, a high-precision immune therapy that uses stem cells and immune cells derived from allogeneic donors to leverage highly purified, polyclonal donor regulatory T-cells to control alloreactive immune responses. The Orca-T manufacturing process retains cells with therapeutic benefits while removing those that pose potential risks. Dr Oliai highlights data from a sub-group analysis of older patients with hematological malignancies enrolled in a multicenter Phase Ib single-arm trial (NCT04013685). These patients were diagnosed with either acute myeloid leukemia (AML), lymphoid or mixed phenotype leukemia, myelodysplastic syndromes (MDS), or chronic myeloid leukemia (CML) in the chronic phase. The participants received a myeloablative regimen of intravenous busulfan, fludarabine, and thiotepa (BFT), followed by Orca-T. Disease outcomes with this treatment approach were very promising, and no transplant-related deaths occurred. This interview took place at the 65th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (edited for clarity)
So this year at ASH, I presented data from Orca-T that shows by using Orca-T, older patients are able to tolerate myeloablative conditioning. Orca-T is a high precision immune therapy that consists of stem and immune cells, derived from an allogeneic donor that leverages a highly purified and polyclonal t-regulatory cell population that’s capable of controlling alloreactive immune responses...
So this year at ASH, I presented data from Orca-T that shows by using Orca-T, older patients are able to tolerate myeloablative conditioning. Orca-T is a high precision immune therapy that consists of stem and immune cells, derived from an allogeneic donor that leverages a highly purified and polyclonal t-regulatory cell population that’s capable of controlling alloreactive immune responses.
So we did a subgroup analysis of a large Phase IB trial in patients who are ages 55 and above who had AML, ALL, or MDS and received orcha-T with myeloablative conditioning busulfan, fludarabine, and thiotepa. There were 25 patients in this subgroup analysis and the median age was 59. We had one year median follow-up, and at one year the disease-free survival was 85%. The transplant related mortality was 0%, and the overall survival was 95%. Only one out of 25 patients developed severe acute graft-versus-host disease.
So there have been other strategies published recently to mitigate transplant-related mortality, mainly by reducing graft-versus-host disease. And then all of these other strategies immunosuppression is increased, for example, triple agent GvH prophylaxis including post-transplant cyclophosphamide or including abatacept.
The orca-T strategy achieves this low transplant-related mortality and low GvH by single agent GvH prophylaxis by using tacrolimus only. So this reduces the pressure on the graft-versus-leukemia effect, and allows for more natural immune reconstitution that preserves the GvL effect. And that’s what we’re seeing the low transplant related mortality and excellent survival. So in this analysis, we have shown that older patients can receive the full curative benefit of myeloablative conditioning by using orca-T.
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Disclosures
Novartis: Research Funding; Jazz Pharmaceuticals: Research Funding; Arog: Research Funding; Seagen: Research Funding; Orca Bio: Research Funding; Pfizer: Research Funding.
