Optimizing Outcomes with Myeloablative Conditioning in Older Patients: Efficacy and Safety of Precision Engineered Orca-T in Patients > 55 Years Old with Hematologic Malignancies

Background Older patients are often deemed unfit for myeloablative conditioning (MAC), which can increase the toxicity associated with transplant, and are relegated to treatment with reduced intensity conditioning (RIC) regimens, which result in a higher incidence of relapse.Orca-T is a high-precision cell therapy biologic that leverages highly purified, polyclonal donor regulatory T cells to control alloreactive immune responses. The specific subsets selected in the Orca-T manufacturing process retain cells with therapeutic benefit while removing those that pose potential risks, allowing for intensification of concomitant chemotherapy and resulting in overall positive outcomes to date in the phase 1b trial. To assess the safety and efficacy in an older patient population, we compared outcomes in those at least 55 years old to younger patients treated with Orca-T. Methods As of 6/02/23, 38 patients ≥18 to <55 (younger) and 25 patients ≥55 years of age (older) received Orca-T as part of a multicenter Phase 1b single-arm trial and had the following diagnosis: AML, ALL, or MPAL in CR/CRi, MDS or CML that was in chronic phase. Patients received MAC consisting of intravenous busulfan, fludarabine, and thiotepa (BFT) prior to Orca-T, followed by single-agent GvHD prophylaxis with tacrolimus, and had an 8/8 related or unrelated matched donor. Results Orca-T was successfully manufactured at a centralized GMP facility, distributed and infused at study sites throughout the U.S. Vein-to-vein time was < 72 hours for all patients, majority < 60 hours.Median age was 47 in the younger group and 59 in the older group. A greater proportion of patients in the younger group had a baseline HCT-CI score of 0 (53%), while more had a baseline HCT-CI score of 4 (12%) in the older group. (Table).Disease free survival at 1 year was similar in both groups at 89% in the younger patients and 86% in the older patients (Figure). Modified GRFS* rate at 12 months among patients in the younger group was 86% compared to 77% in the older group. Non-relapse mortality at 1 year was 0% in both groups who received BFT MAC. Overall survival was 100% and 96% at 12 months in the younger and older patients, respectively.There were two patients > 65 when they received Orca-T; both remain alive without evidence of grade 3-4 acute GvHD, moderate to severe cGvHD, or relapse to date. Conclusions Our analysis suggests that Orca-T cell therapy represents a reduced toxicity alternative to conventional transplant and is well-tolerated by patients 55 and older, with comparable clinical outcomes to those 18 - < 55. In both patient groups, relapse incidence was low, with high GRFS. Remarkably, non-relapse mortality was zero at 1 year with excellent overall survival, suggesting that this regimen could potentially improve outcomes for older patients. An ongoing Phase 3 trial evaluating Orca-T vs. standard of care is currently enrolling throughout the U.S. (NCT05316701).