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Chimeric antigen receptor T-cell therapy for high-grade B-cell lymphoma NOS

Hossain, Nasheed M.
; 
Ahn, Kwang Woo
; 
Patel, Jinalben
; 
Lian, Qinghua
; 
Abid, Muhammad Bilal
; 
Al Nughmush, Ahmed
; 
Bacher, Ulrike
; 
Bi, Xia
; 
Hashmi, Shahrukh K.
; 
Hilal, Talal
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Author
Hossain, Nasheed M.
Ahn, Kwang Woo
Patel, Jinalben
Lian, Qinghua
Abid, Muhammad Bilal
Al Nughmush, Ahmed
Bacher, Ulrike
Bi, Xia
Hashmi, Shahrukh K.
Hilal, Talal
Husnain, Muhammad
Khimani, Farhad
Maziarz, Richard T.
Modi, Dipenkumar
Ram, Ron
Rizzieri, David
Sica, R. Alejandro
Steinberg, Amir
Vij, Ravi
Shadman, Mazyar
Turtle, Cameron
Hamadani, Mehdi
Herrera, Alex F.
Supervisor
Department
Computer Vision
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Type
Journal article
Date
2025
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Language
English
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Abstract
CD19 chimeric antigen receptor T-cell (CAR-T) therapy is a pivotal part of the treatment algorithm for large B-cell lymphoma (LBCL) in the second- and third-line settings based on numerous clinical trials. However, these studies included very few patients with a diagnosis of high-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS) and it is unclear if outcomes are similar to those observed with more common LBCL histologies. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we identified 111 HGBCL-NOS patients who received CAR-T therapy. The cytokine release syndrome (CRS) rate was 74% (7.7% grade 3+), median onset was 4 days (1–17) and immune effector cell-associated neurotoxicity syndrome rate was 45.2% (22.6% grade 3+), median onset was 7 days (1–17). At 2 years post-CAR-T infusion, the probability of overall survival and progression-free survival were 41.6% and 28.7% respectively. The 2-year non-relapse mortality and relapse/progression were 3.1% (95% confidence interval [CI]: 0.6–7.6) and 68.1% (95% CI: 57.9–77.6) respectively. Our analysis illustrates that patients with HGBCL-NOS represent a particularly difficult group to treat, even with CAR-T therapy. We observed that one third of patients achieved a durable response; however, the overall results were less favourable, with lower overall response rate, overall survival and progression-free survival as compared to published reports on LBCL. Graphical Abstract High-grade B-cell lymphoma not otherwise specified (HGBCL-NOS) is a subtype of aggressive B-cell lymphoma that was only recently classified within the past decade. Although CD19 chimeric antigen receptor T-cell (CAR-T) therapy is a pivotal part of the treatment algorithm for large B-cell lymphoma (LBCL), it is unclear if it is as efficacious in HGBCL-NOS. Using the Center for International Blood and Marrow Transplant Research registry, we analysed outcomes in 111 HGBCL-NOS patients who received CAR-T therapy. The overall response rate was 67.6%. The 2-year probability of overall survival and progression-free survival was 41.6% and 28.7% respectively. The 2-year relapse/progression rate was 68.1% (95% CI: 57.9–77.6). Our analysis illustrates that patients with HGBCL-NOS represent a particularly difficult group to treat, even with CAR-T therapy. We observed that one third of patients achieved a durable response; however, the overall results were less favourable with a lower overall response rate, overall survival and progression-free survival as compared to published reports on LBCL.
Citation
N. M. Hossain et al., “Chimeric antigen receptor T-cell therapy for high-grade B-cell lymphoma NOS,” Br J Haematol, 2025, doi: 10.1111/BJH.70020
Source
British journal of haematology
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Publisher
Wiley
DOI
10.1111/bjh.70020
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https://onlinelibrary.wiley.com/doi/10.1111/bjh.70020
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