Unstimulated apheresis for chimeric antigen receptor manufacturing in pediatric/adolescent acute lymphoblastic leukemia patients

Abstract

Autologous unstimulated leukapheresis product serves as starting material for a variety of innovative cell therapy products, including chimeric antigen receptor (CAR)‐modified T‐cells. Although it may be reasonable to assume feasibility and efficiency of apheresis for CAR‐T cell manufacture, several idiosyncrasies of these patients warrant their separate analysis: target cells (mononuclear cells [MNC] and T‐cells) are relatively few which may instruct the selection of apheresis technology, low body weight, and, hence, low total blood volume (TBV) can restrict process and product volume, and patients may be in compromised health. We here report outcome data from 46 consecutive leukaphereses in 33 unique pediatric patients performed for the purpose of CD19‐CAR‐T‐cell manufacturing. Apheresis targets of 2×109 MNC/1×109 T‐cells were defined by marketing authorization holder specification. Patient weight was 8 to 84 kg; TBV was 0.6 to 5.1 L. Spectra Optia apheresis technology was used. For 23 patients, a single apheresis sufficed to generate enough cells and manufacture CAR‐T‐cells, the remainder required two aphereses to meet target dose and/or two apheresis series because of production failure. Aphereses were technically feasible and clinically tolerable without serious adverse effects. The median collection efficiencies for MNC and T‐cells were 53% and 56%, respectively. In summary, CAR apheresis in pediatric patients, including the very young, is feasible, safe and efficient, but the specified cell dose targets can be challenging in smaller children. Continuous monitoring of apheresis outcomes is advocated in order to maintain quality.

Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA)

“…CAR-T product prescription/order and non-mobilised leukapheresis 14,15 scheduling/shipping are coordinated with the CAR-T manufacturing facility (often via proprietary web-based platforms).…”

Relapsed acute lymphoblastic leukaemia after allogeneic stem cell transplantation: a therapeutic dilemma challenging the armamentarium of immunotherapies currently available (case reports)

“…Meeting the specified cell dose targets for successful production of CAR T-cells can be challenging in low-weight infants. 29 Thus far, only few cases have been reported. 12 , 13 …”

Providing the Starting Material to the Manufacturer of an Approved and Commercially Available Autologous CAR-T Cell Treatment

“…Indwelling catheters are suitable (Jarisch et al 2020). -Evaluate whether any form of sedation is necessary (mostly for the paediatric population) through a joint evaluation between the paediatricians and apheresis medical director or practitioner.…”