Outcomes for CART as 2L vs 3L vs 4L or beyond in aggressive B-cell lymphoma: real-world evidence from the ABC Consortium

Chimeric antigen receptor T-cell (CART) therapy has transformed the management of relapsed and refractory large B-cell lymphoma (LBCL), but real-world outcomes data is needed to confirm the benefits seen in clinical trial settings. We performed a multicenter retrospective analysis evaluating CART therapy outcomes according to line of therapy, specifically second line (2L) vs third line (3L) vs fourth line (4L) and beyond (4L+). We included patients who received CD19-directed CART therapy for de novo diffuse LBCL or transformed follicular lymphoma. Overall (N = 466), 21% (n = 98) of patients received CART as 2L, 41% (n = 192) as 3L, and 38% (n = 176) as 4L+. Median follow-up from CART infusion was 35 months. Overall response rate and complete response rate were similar for 2L vs 3L vs 4L+. From CART infusion, median progression-free survival (mPFS) and median overall survival (mOS) were similar for 2L vs 3L, but shorter in patients receiving CART as 4L+ (mPFS, 11.6 vs 12.7 vs 5.7 months, P< .001; mOS, not reached vs 69.4 vs 21.9 months, P< .001). In patients with double-hit or triple-hit lymphoma (DHL/THL), receiving CART in 2L vs 3L significantly improved 3-year OS (63% [2L] vs 32% [3L], P = .01). Patients with disease that required bridging therapy were also at increased risk of progression or death. Overall, our findings inform real-world practice wherein CART therapy as 2L vs 3L yields similar survival outcomes in unselected patients. However, patients specifically with DHL/THL should be considered for CART therapy in the 2L outside of the primary refractory disease (PRD) or early relapsed setting.

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Publication Details

Journal
Blood Advances
Published
2025-11-07
DOI
https://doi.org/10.1182/bloodadvances.2025017120
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
0.00

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article

Outcomes for CART as 2L vs 3L vs 4L or beyond in aggressive B-cell lymphoma: real-world evidence from the ABC Consortium

Reem Karmali, Thomas A. Ollila, Jane N. Winter, Jonathon Brett Cohen et al.
Blood Advances
CAR-T cell therapy research
article

Outcomes for CART as 2L vs 3L vs 4L or beyond in aggressive B-cell lymphoma: real-world evidence from the ABC Consortium

Reem Karmali, Thomas A. Ollila, Jane N. Winter, Jonathon Brett Cohen, Leo I. Gordon, Geoffrey Shouse, Stefan Klaus Barta, Vaishalee Padgaonkar Kenkre, Deborah Marie Stephens, Brian T. Hess, Matthew J Cortese, Ari Pelcovits, Matthew J. Matasar, Jonathan Cruz Moreira, Lindsey A. Fitzgerald, Adam Yuh Lin, Rahul S. Bhansali, Tamara Kay Moyo, Brandon L Ellsworth, Megan Elizabeth Melody, John S. Wang, Christy Jesme, Natalie Sophia Grover, Jason T. Romancik, Megan M. Herr, Shuo Ma, Narendranath Epperla, James A. Davis, Nirav Niranjan Shah, Alexey V. Danilov
article en

Abstract

Chimeric antigen receptor T-cell (CART) therapy has transformed the management of relapsed and refractory large B-cell lymphoma (LBCL), but real-world outcomes data is needed to confirm the benefits seen in clinical trial settings. We performed a multicenter retrospective analysis evaluating CART therapy outcomes according to line of therapy, specifically second line (2L) vs third line (3L) vs fourth line (4L) and beyond (4L+). We included patients who received CD19-directed CART therapy for de novo diffuse LBCL or transformed follicular lymphoma. Overall (N = 466), 21% (n = 98) of patients received CART as 2L, 41% (n = 192) as 3L, and 38% (n = 176) as 4L+. Median follow-up from CART infusion was 35 months. Overall response rate and complete response rate were similar for 2L vs 3L vs 4L+. From CART infusion, median progression-free survival (mPFS) and median overall survival (mOS) were similar for 2L vs 3L, but shorter in patients receiving CART as 4L+ (mPFS, 11.6 vs 12.7 vs 5.7 months, P< .001; mOS, not reached vs 69.4 vs 21.9 months, P< .001). In patients with double-hit or triple-hit lymphoma (DHL/THL), receiving CART in 2L vs 3L significantly improved 3-year OS (63% [2L] vs 32% [3L], P = .01). Patients with disease that required bridging therapy were also at increased risk of progression or death. Overall, our findings inform real-world practice wherein CART therapy as 2L vs 3L yields similar survival outcomes in unselected patients. However, patients specifically with DHL/THL should be considered for CART therapy in the 2L outside of the primary refractory disease (PRD) or early relapsed setting.

Blood AdvancesVol. 10(3)
Rutgers, The State University of New Jersey (US), Northwestern University (US), University of North Carolina at Chapel Hill (US), Roswell Park Comprehensive Cancer Center (US), City Of Hope National Medical Center (US), University of Wisconsin–Madison (US), Emory University (US), Medical University of South Carolina (US), Medical College of Wisconsin (US), University of Utah (US), Brown University (US), Hospital of the University of Pennsylvania (US), The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US), Huntsman Cancer Institute (US), Carolinas Medical Center (US), MUSC Hollings Cancer Center (US), Levine Cancer Institute (US), Northwestern University (PH), University of Wisconsin Carbone Cancer Center (US), City of Hope (US), Lifespan (US), Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Rutgers Cancer Institute (US), UNC Lineberger Comprehensive Cancer Center, University of Pennsylvania (US)
Eli Lilly and Company, Pfizer, AstraZeneca, Gilead Sciences, Celgene, Regeneron Pharmaceuticals, TG Therapeutics, MEI Pharma, BeiGene, Incyte, Seagen, MorphoSys, Ipsen, Genentech, Takeda Oncology, Pharmacyclics, Janssen Biotech, Daiichi Sankyo Europe
Openalex Percentile: Top 55%
CAR-T cell therapy research
DOIOpen Access PDFOpenAlex
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