Update on CAR T-Cell Therapies for Relapsed/Refractory B-Cell Lymphomas

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Stephen J. Schuster
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CAR T cells are genetically engineered to produce an artificial receptor on the T-cell surface for use in immunotherapy, which immediately engages its target, results in CAR T-cell proliferation, and effects target cell cytotoxicity. Prior to CAR T-cell therapy, approximately 30% of patients with diffuse large B-cell lymphoma (DLBCL) had an unmet need for a new treatment approach. There are now 3 commercially available CAR T-cell products capable of achieving long-term, disease-free survival in the third line of therapy for patients with relapsed or refractory DLBCL, transformed follicular lymphoma, or primary mediastinal large B-cell lymphoma: axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel.

Disclosures: Dr. Schuster has disclosed receiving consulting fees from Allogene Therapeutics, AstraZeneca Pharmaceuticals LP, BeiGene, Celgene Corporation, Genentech, Inc., Incyte Corporation, Janssen Pharmaceutica Products, LP, Legend Biotech, Loxo Oncology, Onc., Novartis Pharmaceuticals Corporation, and Regeneron Pharmaceuticals, Inc.; serving as a scientific advisor for Celgene Corporation, Genentech, Inc., Loxo Oncology, Onc., and Novartis Pharmaceuticals Corporation; receiving grant/research support from Genentech, Inc. and Novartis Pharmaceuticals Corporation; and receiving honoraria from Novartis Pharmaceuticals Corporation.

Correspondence: Stephen J. Schuster, MD, Abramson Cancer Center at the University of Pennsylvania, 3400 Civic Center Boulevard, PCAM, Floor 12, Room 12-178, Philadelphia, PA 19104. Email: schustes@pennmedicine.upenn.edu
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  • 1.

    Locke FL , Ghobadi A , Jacobson CA , et al.. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1–2 trial. Lancet Oncol 2019;20:3142.

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  • 2.

    Schuster SJ , Bishop MR , Tam CS , et al.. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med 2019;380:4556.

  • 3.

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  • 4.

    Neelapu SS , Locke FL , Bartlett NL , et al.. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 2017;377:25312544.

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  • 5.

    Schuster SJ , Maziarz RT , Rusch ES , et al.. Grading and management of cytokine release syndrome in patients treated with tisagenlecleucel in the JULIET trial. Blood Adv 2020;4:14321439.

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