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

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 therap...

Full description

Saved in:
Bibliographic Details
Main Authors: Alejandro Luna, Sean M. Devlin, Kai Rejeski, Jessica R. Flynn, Magdalena Corona, Efrat Luttwak, Alfredo Rivas-Delgado, Ivan Landego, Giulio Cassanello, Marina Gomez-Llobell, Sandeep S. Raj, Parastoo B. Dahi, Richard J. Lin, Allison Parascondola, M.Lia Palomba, Gunjan L. Shah, Michael Scordo, Ana Alarcon Tomas, Doris Leithner, Akshay Bedmutha, Heiko Schöder, Brandon S. Imber, Gilles Salles, Jae H. Park, Miguel-Angel Perales, Roni Shouval
Format: Article
Language:English
Published: Nature Publishing Group 2025-04-01
Series:Blood Cancer Journal
Online Access:https://doi.org/10.1038/s41408-025-01273-1
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Differential site-specific response and relapse/progression risk according to pre-CAR-T therapy anatomical site involvement in Large B-cell Lymphoma. Risk of site-specific relapse or progression was not evaluable for CNS/orbital/cranial sinuses, adrenal/genitourinary, hepatobiliary/pancreas, and spleen due to insufficient number of events.
ISSN:2044-5385

Similar Items