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

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.

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Publication Details

Journal
Blood Cancer Journal
Published
2025-04-14
DOI
https://doi.org/10.1038/s41408-025-01273-1
Citations
3
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
3.14

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article

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

Efrat Luttwak, Heiko M. Schöder, Marina Gómez-Llobell, Gunjan L. Shah et al.
3 citations
Blood Cancer Journal
CAR-T cell therapy research
3.14
article

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

Efrat Luttwak, Heiko M. Schöder, Marina Gómez-Llobell, Gunjan L. Shah, Richard J. Lin, Brandon S. Imber, Magdalena Corona, Giulio Cassanello, Ivan Landego, Roni Shouval, Akshay Bedmutha, Sean M. Devlin, Parastoo Bahrami Dahi, Michael Scordo, Doris Leithner, Maria Lia Palomba, Kai Rejeski, Sandeep S. Raj, Alfredo Rivas‐Delgado, Allison Parascondola, Alejandro Luna, Miguel‐Angel Perales, Gilles Salles, Jessica Flynn, Ana Alarcón Tomás, Jae H. Park
article en
3 citations

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.

Blood Cancer JournalVol. 15(1)
Memorial Sloan Kettering Cancer Center (US), Cornell University (US), LMU Klinikum (DE), Hospital Universitario 12 De Octubre (ES), Hospital Universitario Puerta de Hierro Majadahonda (ES), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Hospital Universitario Ramón y Cajal (ES), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), Ludwig-Maximilians-Universität München (DE)
Lymphoma Research Foundation, Gilead Sciences, Memorial Sloan-Kettering Cancer Center, Swim Across America, Fundación Española de Hematología y Hemoterapia, National Institutes of Health, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 8%
CAR-T cell therapy research
3.14
DOIOpen Access PDFOpenAlex
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