Cost-Effectiveness of Orca-T Vs Allo-HCT with Conventional GVHD Prophylaxis for the Treatment of Advanced Hematologic Malignancies in the United States

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for patients with hematologic malignancies, but its success is limited by GVHD, which is associated with substantial morbidity, mortality, and economic burden. Orca-T, an investigational, high-precision cell therapy, demonstrated improvement in survival free of moderate-to-severe chronic GVHD compared to conventional allo-HCT with tacrolimus/methotrexate (TAC/MTX) in the pivotal Phase 3 Precision- T trial. Given the rising costs of GVHD therapies and the long-term care burden, assessing the economic value of Orca-T is essential. To assess the cost effectiveness of Orca-T compared to conventional allo-HCT with TAC/MTX GVHD prophylaxis from a US health system perspective. A three-state partitioned survival model (relapse-free, relapsed, and dead) with monthly cycles and a lifetime horizon was developed. The intervention arm included Orca-T with single-agent tacrolimus, while the comparator arm included conventional allo-HCT with TAC/MTX GVHD prophylaxis. Overall survival and relapse-free survival data from the Phase 3 Precision-T study were incorporated using a cure-mixture modeling approach to estimate long-term survival and relapse status for patients. Costs included conditioning regimens, index procedure length of stay, Orca-T acquisition, donor procurement (conventional allo-HCT with TAC/MTX only), acute GVHD (aGVHD) and chronic GVHD (cGVHD) management, infection management, and terminal care. Model outcomes included life-years, quality-adjusted life-years (QALYs), and direct healthcare costs. Both costs and outcomes were discounted at 3% annually. Orca-T was associated with lower lifetime costs of $1,412,864 compared to $2,253,413 for conventional allo-HCT with TAC/MTX with a lifetime cost savings of $840,548 per patient. The costs associated with Orca-T acquisition were offset by savings from aGVHD, infection, and cGVHD management costs. The cGVHD management costs were $735,974 for Orca-T compared to $1,984,702 for conventional allo-HCT with TAC/MTX. Orca-T was also associated with 15.80 QALYs compared to 11.45 QALYs with conventional allo-HCT with TAC/MTX over a patient's lifetime. Given the combination of cost savings and QALY gains, Orca-T is dominant over conventional allo-HCT with TAC/MTX. Over a patient's lifetime, the model demonstrated that Orca-T can reduce the overall economic burden compared to conventional allo-HCT with TAC/MTX, with the majority of cost savings driven by reductions in aGVHD, infection, and cGVHD management costs. Given the considerable clinical and economic impact of these complications, Orca-T represents a high value therapeutic option for adults with advanced hematologic malignancies, offering both superior clinical outcomes and economic benefits.