Collection efficiency and safety of large‐volume leukapheresis for the manufacturing of tisagenlecleucel

Abstract Background In patients with relapsed or refractory B cell acute lymphoblastic leukemia or B cell non‐Hodgkin lymphoma (r/r B‐ALL/B‐NHL) with low CD3 + cells in the peripheral blood (PB), sufficient CD3 + cell yield in a single day may not be obtained with normal‐volume leukapheresis (NVL). Large‐volume leukapheresis (LVL) refers to the processing of more than three times the total blood volume (TBV) in a single session for PB apheresis; however, the efficiency and safety of LVL for manufacturing of tisagenlecleucel (tisa‐cel) remain unclear. This study aimed to investigate the tolerability of LVL. Study Design and Methods We retrospectively collected data on LVL (≥3‐fold TBV) and NVL (<3‐fold TBV) performed for patients with r/r B‐ALL/B‐NHL in our institution during November 2019 and September 2023. All procedures were performed using a continuous mononuclear cell collection (cMNC) protocol with the Spectra Optia. Results Although pre‐apheresis CD3 + cells in the PB were significantly lower in LVL procedures (900 vs. 348/μL, p < .01), all patients could obtain sufficient CD3 + cell yield in a single day with a comparably successful rate of final products (including out‐of‐specification) between the two groups (97.2% vs. 100.0%, p = 1.00). The incidence and severity of citrate toxicity (no patients with grade ≥ 3) during procedures was not significantly different between the two groups (22.2% vs. 26.1%, p = .43) and no patient discontinued leukapheresis due to any complications. Conclusion LVL procedures using Spectra Optia cMNC protocol was well tolerated and did not affect the manufacturing of tisa‐cel.