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
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.
Author
Dulobdas, Vaishali
Kirkwood, Amy A
Serpenti, Fabio
Gautama, Brijesh
Panopoulou, Aikaterini
Mathew, Amrith
Gabriel, Sumantha
Malladi, Ram
Pealing, Jessica
Bonney, Denise
Nicholson, Emma
Besley, Caroline
Ghorashian, Sara
Kuhnl, Andrea
Davies, Elizabeth
Chappell, Jackie
Black, Anne
Menne, Tobias
O'Reilly, Maeve A
Sanderson, Robin
Chaganti, Sridhar
Kirkwood, Amy A
Serpenti, Fabio
Gautama, Brijesh
Panopoulou, Aikaterini
Mathew, Amrith
Gabriel, Sumantha
Malladi, Ram
Pealing, Jessica
Bonney, Denise
Nicholson, Emma
Besley, Caroline
Ghorashian, Sara
Kuhnl, Andrea
Davies, Elizabeth
Chappell, Jackie
Black, Anne
Menne, Tobias
O'Reilly, Maeve A
Sanderson, Robin
Chaganti, Sridhar
Date
2025-03-04
Type
Article
Subject
pharmacy, Lymphoma
Collections
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
Journal / Source Title
Blood cancer journal
DOI
10.1038/s41408-025-01225-9
PMID
40032870
Publisher
Nature Publishing Group