Risk factors for CAR T-cell manufacturing failure and patient outcomes in large B-cell lymphoma: a report from the UK National CAR T Panel
Dulobdas, Vaishali Kirkwood, Amy A Serpenti, Fabio Gautama, Brijesh Panopoulou, Aikaterini Mathew, Amrith Gabriel, Sumantha Malladi, Ram Pealing, Jessica Bonney, Denise
Dulobdas, Vaishali
Kirkwood, Amy A
Serpenti, Fabio
Gautama, Brijesh
Panopoulou, Aikaterini
Mathew, Amrith
Gabriel, Sumantha
Malladi, Ram
Pealing, Jessica
Bonney, Denise
Affiliation
Other Contributors
Publication date
2025-03-04
Collections
Research Projects
Organizational Units
Journal Issue
Abstract
CAR T-cell manufacturing failure (MF) is a situation where the manufacturing process fails to yield a product or results in one which is out-of-specification (OOS). We conducted a multicentre retrospective review of factors contributing to MF and patient outcomes. Of 981 large B-cell lymphoma (LBCL) patients approved for CAR T-cell therapy, 38 (3.87%) had MF. Eleven patients received delayed infusion with a product in-specification (delayed-infused) following 21 remanufacturing attempts. OOS product was infused in 13 (OOS-infused), and 14 were not infused. For comparison, we included 38 LBCL controls without MF; 29 received infusion (controls-infused). Prior bendamustine was the only baseline variable associated with MF risk, largely due to therapy within 6 months; 23.7% MF vs 0% controls (P = 0.0029). Overall survival (OS) and progression-free survival (PFS) were not significantly different for infused patients, with 1-year OS (PFS) of 52.8% (46.2%), 46.8% (24.2%) and 68.4% (41.4%) for OOS-infused, delayed-infused and controls-infused respectively (PFS HR OOS-infused vs controls-infused 1.41, P = 0.40; delayed-infused vs controls-infused 1.64, P = 0.25; and OOS-infused vs delayed-infused 0.86, P = 0.76). CRS, ICANS and cytopenias were not significantly different between cohorts. Outcomes for OOS-infused LBCL patients following MF are encouraging. Remanufacturing led to infusion of a product in-specification in around 50% and may be an option for patients where a suitable OOS product is not available.
Citation
Dulobdas V, Kirkwood AA, Serpenti F, Gautama B, Panopoulou A, Mathew A, Gabriel S, Malladi R, Pealing J, Bonney D, Nicholson E, Besley C, Ghorashian S, Kuhnl A, Davies E, Chappell J, Black A, Menne T, O'Reilly MA, Sanderson R, Chaganti S. Risk factors for CAR T-cell manufacturing failure and patient outcomes in large B-cell lymphoma: a report from the UK National CAR T Panel. Blood Cancer J. 2025 Mar 4;15(1):30. doi: 10.1038/s41408-025-01225-9
Type
Article