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Strategies following failure of CAR-T-cell therapy in non-Hodgkin lymphoma

Bone Marrow Transplantation volume 60, pages 182–190 (2025)Cite this article

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Abstract

Several CD19 CAR-T-cell drugs are approved for safety and efficacy in advanced B-cell cancers with encouraging results. However, primary refractory and relapse are common. We critically analyze long-term data on efficacy of CD19 CAR-T-cell therapies in B-cell non-Hodgkin lymphomas from clinical trials with those of so-called real world data. We identify co-variates associated with efficacy, discuss mechanisms of relapse, summarize the data on the results of post-failure therapy including allotransplants, monoclonal and bi-specific antibodies, antibody-drug conjugates, immune checkpoint-inhibitors and repeat infusions of CAR-T-cells. We conclude, save for allotransplants, there are few data strongly supporting any of these interventions. Most trial are with few heterogeneously-treated subjects with diverse interventions and brief follow-up. Interventions need to be tailored to the cause(s) of CAR-T-cell failure. Prestly, there is not a convincingly safe and effective therapy of people failing initial CAR-T-cell therapy of B-cell non-Hodgkin lymphoma.

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Fig. 1: Mechanisms of relapse in CD19 CAR-T-cell therapy.

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Acknowledgements

RPG acknowledges support from the UK National Institute of Health Research (NIHR) Biomedical Research Center.

Funding

Supported, in part, by grants from the National Natural Science Foundation of China (82370218 to BP, 82341203 to KX) and Jiangsu Provincial Key Research and Development Program (BE2021631 to BP).

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Authors and Affiliations

  1. Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China

    Xiaotian Zhang, Kailin Xu & Bin Pan

  2. Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China

    Xiaotian Zhang, Kailin Xu & Bin Pan

  3. Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, England

    Robert Peter Gale

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  1. Xiaotian Zhang
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  2. Kailin Xu
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  3. Robert Peter Gale
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  4. Bin Pan
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BP contributed to the concept, analyzed data and revised the manuscript. KX contributed to the concept and revised the manuscript. XZ did literature retrieval and wrote the manuscript. RPG helped analyze data and revised the manuscript.

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Correspondence to Kailin Xu or Bin Pan.

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RPG is a consultant to Antengene Biotech LLC; Medical Director, FFF Enterprises Inc.; A speaker for Janssen Pharma and Hengrui Pharma; Board of Directors: Russian Foundation for Cancer Research Support and Scientific Advisory Board, StemRad Ltd.

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Zhang, X., Xu, K., Gale, R.P. et al. Strategies following failure of CAR-T-cell therapy in non-Hodgkin lymphoma. Bone Marrow Transplant 60, 182–190 (2025). https://doi.org/10.1038/s41409-024-02463-4

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