Synapse - CAR T-cell therapy response varies by extranodal disease site in large B-cell lymphoma

CAR T-cell therapy response varies by extranodal disease site in large B-cell lymphoma Journal Article

Authors:	Luna, A.; Devlin, S. M.; Rejeski, K.; Flynn, J. R.; Corona, M.; Luttwak, E.; Rivas-Delgado, A.; Landego, I.; Cassanello, G.; Gomez-Llobell, M.; Raj, S. S.; Dahi, P. B.; Lin, R. J.; Parascondola, A.; Palomba, M.; Shah, G. L.; Scordo, M.; Alarcon Tomas, A.; Leithner, D.; Bedmutha, A.; Schöder, H.; Imber, B. S.; Salles, G.; Park, J. H.; Perales, M. A.; Shouval, R.
Article Title:	CAR T-cell therapy response varies by extranodal disease site in large B-cell lymphoma
Abstract:	The role of extranodal (EN) sites as potential sanctuary regions resistant to CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy in large B-cell lymphoma (LBCL) remains unclear. To investigate this, we retrospectively analyzed 283 adults treated with commercial CD19 CAR-T therapy, assessing 958 PET-CT scans across four time points: pre-apheresis, pre-lymphodepletion, best response, and relapse. EN involvement prior to CAR-T therapy was common (76%). Outcomes for patients with exclusive EN disease were similar to those with nodal (ND) disease alone; however, patients with concomitant EN and ND disease (EN + ND) had lower complete response rates and shorter progression-free survival. Site-specific outcomes varied: lungs/pleura/pericardium and gastrointestinal/peritoneum involvement had the lowest local response rates (48% and 51%, respectively). Notably, the risk of same-site relapse was highest in the lungs/pleura/pericardium (hazard ratio [HR] 7.8) and gastrointestinal/peritoneum (HR 5.97). Among patients relapsing after CAR-T, two-year overall survival rates from time of relapse were significantly lower in those with EN relapse (23% for exclusive EN; 25% for EN + ND) compared to exclusive ND relapse (64%; p = 0.008). These findings underscore the high prevalence of EN disease in CAR-T recipients and its site-specific impact on outcomes, highlighting the need for organ-targeted strategies to enhance treatment efficacy. (Figure presented.) © The Author(s) 2025.
Journal Title:	Blood Cancer Journal
Volume:	15
ISSN:	2044-5385
Publisher:	Nature Publishing Group
Date Published:	2025-04-14
Start Page:	64
Language:	English
DOI:	10.1038/s41408-025-01273-1
PROVIDER:	scopus
PMCID:	PMC11997148
PUBMED:	40229268
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-105003143857&doi=10.1038%2fs41408-025-01273-1&partnerID=40&md5=ea30bf3c188be0a8c1bf115bfe32df2b
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Roni Shouval -- Source: Scopus