Researchers found that prior use of bendamustine within six months of apheresis was the only baseline variable associated with a risk of manufacturing failure in patients approved for treatment with a chimeric antigen receptor (CAR) T-cell therapy.
The study was led by Vaishali Dulobdas, MD, of the University Hospitals Birmingham National Health Service (NHS) Foundation Trust in the United Kingdom, and published in Blood Cancer Journal.
The multicenter, retrospective study collected data from nine CAR-T centers in the United Kingdom and assessed risk factors associated with manufacturing failure as well as patient outcomes.
CAR-T manufacturing failure
In a cohort of 981 patients with relapsed or refractory large B-cell lymphoma (LBCL) who were approved for CAR T-cell therapy (axicabtagene ciloleucel or tisagenlecleucel) between January 2019 and January 2023, 38 (3.87%) experienced manufacturing failure, which was defined as unavailability of in-specification CAR-T product.
Eleven patients received delayed infusion with a product in-specification after 21 remanufacturing attempts. Thirteen patients received out-of-specification (OOS) product, and 14 were not infused.
The researchers included a cohort of 38 controls with LBCL who did not experience manufacturing failure, 29 of whom received infusion.
Response and toxicity did not appear to significantly differ among OOS-infused, delayed-infused, or control-infused patients.
Overall survival (OS) and progression-free survival (PFS) were not significantly impacted for infused patients, with one-year OS rates of 52.8%, 46.8%, and 68.4% for OOS-infused, delayed-infused, and control-infused patients, respectively. One-year PFS rates were 46.2%, 24.2%, and 41.4%, respectively.
Rates of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and cytopenia were not significantly different across cohorts.
The researchers noted that the study is limited by its small patient population, and the patients were heavily pretreated (approved for third-line or beyond CAR-T). They also reported that the risk of manufacturing failure may be different in less heavily treated patients. Remanufacturing led to infusion of a product in-specification only half of the time.
“Our results suggest encouraging outcomes for patients infused with an OOS product comparable to control patients without manufacturing failure infused with a product in-specification,” the authors concluded.
Reference
Dulobdas V, Kirkwood AA, Serpenti F, et al. 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;15(1):30. doi:10.1038/s41408-025-01225-9
