. 2025 Sep;207(3):1011-1018.

doi: 10.1111/bjh.70020. Epub 2025 Jul 22.

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

Nasheed M Hossain¹, Kwang Woo Ahn², Jinalben Patel³, Qinghua Lian³, Muhammad Bilal Abid⁴, Ahmed Al Nughmush⁵, Ulrike Bacher⁶, Xia Bi⁷, Shahrukh K Hashmi^{8

9}, Talal Hilal¹⁰, Muhammad Husnain¹¹, Farhad Khimani¹², Richard T Maziarz¹³, Dipenkumar Modi¹⁴, Ron Ram¹⁵, David Rizzieri¹⁶, R Alejandro Sica¹⁷, Amir Steinberg¹⁸, Ravi Vij¹⁹, Mazyar Shadman²⁰, Cameron Turtle^{21

22}, Mehdi Hamadani²³, Alex F Herrera²⁴

Affiliations

¹ Division of Hematology/Oncology-Cell Therapy and Transplant Program, University of Pennsylvania-Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
² Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
³ CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
⁴ The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, Texas, USA.
⁵ Department of Hematology, Stem Cell Transplant and Cellular Therapy, Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
⁶ Department of Hematology, Inselspital, University Hospital and University of Bern, Bern, Switzerland.
⁷ Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
⁸ Mayo Clinic, Rochester, Minnesota, USA.
⁹ SSMC, Abu Dhabi, UAE.
¹⁰ Mayo Clinic, Phoenix, Arizona, USA.
¹¹ Division of Hematology/Oncology, Banner University of Arizona, Medical Center, Tucson, Arizona, USA.
¹² Moffitt Cancer Center, Tampa, Florida, USA.
¹³ Knight Cancer Institute-Oregon Health and Science University, Portland, Oregon, USA.
¹⁴ Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
¹⁵ Hematology Department-Tel Aviv (Sourasky) Medical Center, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv-Yafo, Israel.
¹⁶ Novant Health Cancer Institute, Charlotte, North Carolina, USA.
¹⁷ Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York, USA.
¹⁸ New York Medical College, Valhalla, New York, USA.
¹⁹ Division of Medical Oncology, Washington University in St Louis, St. Louis, Missouri, USA.
²⁰ University of Washington, Seattle, Washington, USA.
²¹ University of Sydney School of Medicine, Sydney, New South Wales, Australia.
²² Royal North Shore Hospital, Sydney, New South Wales, Australia.
²³ Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
²⁴ City of Hope National Medical Center, Duarte, California, USA.

PMID: 40693472
PMCID: PMC12705125
DOI: 10.1111/bjh.70020

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

Nasheed M Hossain et al. Br J Haematol. 2025 Sep.

. 2025 Sep;207(3):1011-1018.

doi: 10.1111/bjh.70020. Epub 2025 Jul 22.

Authors

Affiliations

¹ Division of Hematology/Oncology-Cell Therapy and Transplant Program, University of Pennsylvania-Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
² Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
³ CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
⁴ The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, Texas, USA.
⁵ Department of Hematology, Stem Cell Transplant and Cellular Therapy, Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
⁶ Department of Hematology, Inselspital, University Hospital and University of Bern, Bern, Switzerland.
⁷ Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
⁸ Mayo Clinic, Rochester, Minnesota, USA.
⁹ SSMC, Abu Dhabi, UAE.
¹⁰ Mayo Clinic, Phoenix, Arizona, USA.
¹¹ Division of Hematology/Oncology, Banner University of Arizona, Medical Center, Tucson, Arizona, USA.
¹² Moffitt Cancer Center, Tampa, Florida, USA.
¹³ Knight Cancer Institute-Oregon Health and Science University, Portland, Oregon, USA.
¹⁴ Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
¹⁵ Hematology Department-Tel Aviv (Sourasky) Medical Center, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv-Yafo, Israel.
¹⁶ Novant Health Cancer Institute, Charlotte, North Carolina, USA.
¹⁷ Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York, USA.
¹⁸ New York Medical College, Valhalla, New York, USA.
¹⁹ Division of Medical Oncology, Washington University in St Louis, St. Louis, Missouri, USA.
²⁰ University of Washington, Seattle, Washington, USA.
²¹ University of Sydney School of Medicine, Sydney, New South Wales, Australia.
²² Royal North Shore Hospital, Sydney, New South Wales, Australia.
²³ Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
²⁴ City of Hope National Medical Center, Duarte, California, USA.

PMID: 40693472
PMCID: PMC12705125
DOI: 10.1111/bjh.70020

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.

Keywords: chimeric antigen receptor T cell therapy; lymphomas; non‐Hodgkin lymphoma.

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Conflict of interest statement

Disclosure of conflict of interest:

Mehdi Hamadani reports research support/Funding: ADC Therapeutics; Spectrum Pharmaceuticals; Astellas Pharma. Consultancy: ADC Therapeutics, Omeros, CRISPR, BMS, Kite, AbbVie, Caribou, Genmab, Autolus, Forte Biosciences, Byondis, Allovir, Poseidon. Speaker’s Bureau: ADC Therapeutics, AstraZeneca, Bei Gene, Kite, Sobi. DMC: Inc, Genentech, Myeloid Therapeutics, CRISPR

David Rizzieri: None

Muhammad Husnain: Consultancy Kite Pharma

R. Alejandro Sica: Kite Pharma research funding

Shahrukh K. Hashmi: None

Ulrike Bacher: None

Ravi Vij: None

Talal Hilal: None

Ron Ram: None declared?

Ahmed Al Nughmush: None

Dipenkumar Modi: Consulting/advisory role: ADC therapeutics, Genmab, Genentech (spouse), Daiichi Sankyo (spouse), AstraZeneca (spouse)

Research funding for IITs: Genentech, Genmab, Karyopharm, AstraZeneca (spouse)

Expert testimony: AstraZeneca

Farhad KhimaniI: None declared?

Xia Bi: Research funding from BMS and Incyte

Bilal Abid: None Richard T. Maziarz: Research support from Novartis, Gilead/Kite, BMS/Celgene/JunoServed as consultant for Oricell, Autolus Therapeutics, Incyte and Miltenyi. On Scientific Advisory Board for Artiva Therapeutics and Oricell. Currently active on DSMB panels for March Therapeutics, Century Therapeutics and Vor Pharmaceuticals.

Amir Steinberg: None

Alex F. Herrera: Research funding: Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca; Consultancy: Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca, ADC Therapeutics, Takeda, Genmab, Pfizer, Abbvie, Allogene Therapeutics

The other authors reported no conflicts of interest to disclose.

Figures

**Figure 1 –**
OS/PFS/Relapse Plots for HBCL-NOS Post CAR-T

**FIGURE 2-**
Univariate Analysis for OS, PFS and Relapse risk in HGBCL Post CAR-T

See this image and copyright information in PMC

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

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

Authors

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Conflict of interest statement

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