Apheresis for chimeric antigen receptor T-cell production in adult lymphoma patients

Abstract

Background: To date, in-depth analysis of leukapheresis products as starting material for CAR T-cell manufacturing, specifically Tisagenlecleucel production, are scarce. In this study, we report on lymphapheresis data for production of Tisagenlecleucel for elderly and pretreated lymphoma patients. Study Design and Methods: Spectra Optia from Terumo BCT, Lakewood, CO, was employed for apheresis using the cMNC program. Apheresis success was defined as meeting a target total nucleated cell (TNC) count of ≥2 × 109, a CD3-positive lymphocyte count of ≥1 × 109 and an overall viability of ≥70% in the lymphapheresis product. Results: Twenty-three patients (age 37–77 years) and 24 apheresis runs were evaluated. The median CD3-positive lymphocyte count in peripheral blood at the beginning of apheresis was 565 cells/μl (range: 70–1345 cells/μl). Circulating lymphoma cells were detected in one patient prior to apheresis. Target criteria were met in 21 of 23 patients. The median TNC count in the apheresate was 11.2 × 109 (range: 2.9 × 109–47.4 × 109). The median CD3-positive lymphocyte count in the apheresate was 2.55 × 109 (range: 0.370 × 109–6.915 × 109), which resulted in a median collection efficiency for CD3-positive lymphocytes of 63.7% (range: 9.56%–93.6%). No adverse events associated with the apheresis process were observed. Conclusions: Lymphapheresis with the Spectra Optia cMNC program provided a sufficient quantity of CD3-positive lymphocytes for CAR T-cell manufacturing for the majority of patients despite their heavy pretreatment and advanced age. Moreover, we are the first to advocate early pre-emptive lymphocyte collection in DLBCL-NOS patients intended to undergo treatment with Tisagenlecleucel.