Yield-driven approach optimizes apheresis of CD19 chimeric antigen receptor-T cell therapy for patients with lymphoma

Leukapheresis for chimeric antigen receptor (CAR) T cell therapy requires optimization according to product-specific manufacturing requirements. We retrospectively analyzed 80 patients with large B-cell lymphoma, who underwent leukapheresis for tisagenlecleucel (tisa-cel, n = 31), lisocabtagene maraleucel (liso-cel, n = 29) or axicabtagene ciloleucel (axi-cel, n = 20) at Kyoto University Hospital between January 2022 and October 2024. Peripheral blood (PB) CD3⁺ cell counts before leukapheresis (median, 504/μL) and collection efficiencies (median, 62.1%) were similar among groups. The axi-cel group required significantly larger processing blood volumes (axi-cel, 12 L; liso-cel, 12 L; tisa-cel, 10 L; P < 0.001) and longer processing times (axi-cel, 240 min; liso-cel, 204 min; tisa-cel, 203 min; P = 0.002), resulting in higher CD3⁺ cell yields. Moreover, the standard deviation of CD3⁺ cell yields was significantly larger in the axi-cel group (axi-cel, 3.04 × 10⁹ cells; liso-cel, 1.54 × 10⁹ cells; tisa-cel, 1.59 × 10⁹ cells; P = 0.003). The axi-cel group more frequently exceeded estimated blood volumes needed to achieve 5 × 10⁹ CD3⁺ cells (axi-cel, 45.0%; liso-cel, 17.2%; tisa-cel, 16.1%; P = 0.048). These findings highlight variability in leukapheresis procedures among CAR-T products. Protocols targeting cell yields based on PB cell counts may optimize blood volume to be processed so as to reduce patient burden.