Individualizing Apheresis Processing Volumes Using a Predictive Algorithm: Analysis of the CAR T‐Cell Collection Protocol Utilized in ACIT001 / EXC002 , a Phase Ib/ II Trial of Decentralized Production of CAR T Cells for Treatment of Relapsed/Refractory Aggressive NHL and ALL

Chimeric antigen receptor (CAR) T‐cell therapy has become an established treatment for relapsed or refractory B‐cell malignancies. Apheresis collection of peripheral blood mononuclear cells (PBMCs) is a critical first step in CAR T‐cell manufacturing. However, the total blood volume (TBV) required to achieve adequate T‐cell yield is difficult to predict. As a result, standard practice often involves processing two to four TBVs, which may lead to unnecessary time on machine (TOM) and increased risk of procedure‐related complications such as citrate toxicity, hypovolemia, and thrombocytopenia. As part of the ACIT001/EXC002 clinical trial evaluating point‐of‐care CAR T‐cell manufacturing for relapsed/refractory non‐Hodgkin lymphoma (NHL) or acute lymphoblastic leukemia (ALL), we developed a pragmatic protocol to individualize TBV processing. This protocol uses a preliminary TBV estimate based on an assumed CD3‐positive T‐cell collection efficiency (CE) of 50%, followed by a midpoint product assessment to measure actual CE and adjust the remaining TBV and TOM. Using this approach, the preliminary estimate was adequate or conservative in 72% of procedures, and over 75% of patients required less than the standard two to four TBVs. The target CD3‐positive T‐cell yield was achieved in 93% of patients. These findings demonstrate that a midpoint‐adjusted TBV calculation protocol can minimize unnecessary TOM while maintaining reliable T‐cell collection, thereby improving resource utilization and patient safety. Trial Registration ClinicalTrials.gov identifier: NCT03938987