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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, V. Kirkwood, A. A. Serpenti, F. Gautama, B. Panopoulou, A. Mathew, A. Gabriel, S. Malladi, R. Pealing, J. Bonney, D.
Dulobdas, V.
Kirkwood, A. A.
Serpenti, F.
Gautama, B.
Panopoulou, A.
Mathew, A.
Gabriel, S.
Malladi, R.
Pealing, J.
Bonney, D.
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 (Pā=ā0.0029). 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, Pā=ā0.40; delayed-infused vs controls-infused 1.64, Pā=ā0.25; and OOS-infused vs delayed-infused 0.86, Pā=ā0.76). 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.
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2025
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Dulobdas V, Kirkwood AA, Serpenti F, Gautama B, Panopoulou A, Mathew A, 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 Mar 4;15(1):30. PubMed PMID: 40032870. Pubmed Central PMCID: PMC11876324 and Abbvie and honoraria from Abbvie. AAK has received honoraria from Kite-Gilead and Janssen. BG has received honoraria from Kite-Gilead and travel support from Kite-Gilead and Janssen. ED has received honoraria from Kite-Gilead. AP has received meeting attendance support from Kite-Gilead. SG has received honoraria from Accord, Janssen, Pfizer, Abbvie and Kite-Gilead. RM has received honoraria from Novartis and Kite-Gilead and travel support from Kite-Gilead. EN has received honoraria from Novartis, BMS-Celgene and Kite-Gilead and travel support from Kite-Gilead and research grant from Kite-Gilead. CB has received honoraria from Kite-Gilead, Novartis, Janssen and Takeda and travel support from Kite-Gilead and Janssen. SG has received honoraria from Novartis and holds patents and Royalties with UCLB. AK has received honoraria from Kite/Gilead, Roche, BMS, Abbvie and travel sponsorship from Kite/Gilead and AstraZeneca. JC has received honoraria from Abbvie, Miltenyi Biotec and Vertex. AB has received honoraria from Pierre fabre and Kite-Gilead. TM has received honoraria from Kite-Gilead, Amgen, Novartis, Pfizer, Celgene-BMS, Daiichi Sankyo, Atara, Roche, Janssen; Research Funding from Janssen, AstraZeneca, Novartis; Travel grants from Amgen, Jazz, Pfizer, Bayer, Kyowa Kirin, Celgene-BMS, Kite-Gilead, Janssen, Takeda; Speaker fee from Kite/Gilead, Takeda, Janssen, F. Hoffmann-La Roche Ltd, Servier, Novartis, Celgene/BMS, Pfizer, Incyte; Divested equity in a private or publicly-traded company in the past 24 months, Kite/Gilead, Amgen, Novartis, Pfizer, Celgene/BMS, Daiichi Sankyo, Atara, F. Hoffmann-La Roche Ltd, Janssen, BMS, CTI BioPharma, Blueprint Medicines, Sanofi-Aventis, Spark Therapeutics. M OāR has received honoraria from Autolus Janssen, Kite-Gilead and Novartis, advisory board for Kite-Gilead and Autolus and travel grant from Kite-Gilead. RS has received honoraria from Novartis, Kite-Gilead, AstraZeneca and Abbvie and meeting attendance support from Kite-Gilead and AstraZeneca. SC has received honoraria from Takeda, Kite/Gilead, Incyte, AbbVie, Pierre Fabre: F. Hoffmann-La Roche Ltd, Atara Bio, Orion Pharma, Adicet Bio, Incyte, Novartis, Amgen, Sobi, Pierre Fabre, BMS-Celgene and Miltenyi Biotec and meeting attendance support from Takeda, Kite-Gilead, Abbvie, and Pierre Fabre. FS and AM have no competing interests. Ethics approval and consent to participate: This retrospective study was part of a national service evaluation exercise on behalf of the NHS England OOS CAR T Clinical Panel, not requiring separate ethics approval. Patients were consented for deidentified or pseudo-anonymised data collection and sharing as per institutional protocols. The study was conducted in accordance with relevant guidelines and regulations. Epub 2025/03/04. eng.