CAR-T IMMUNOTHERAPY IN VARIOUS LYMPHOMAS – AN OVERVIEW INCLUDING THE LATEST STUDIES FROM 2017–2025
Abstract
The review presents the development and current applications of CAR-T (chimeric antigen receptor T-cell therapy) in the treatment of various forms of non-Hodgkin's lymphoma between 2017 and 2025. CAR-T cell immunotherapy, based on the genetic modification of the patient's autologous T cells to recognize the CD19 antigen, has revolutionized the treatment of lymphomas resistant to standard methods. Major clinical trials, such as, have confirmed the high efficacy of CAR-T therapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The complete remission (CR) rates achieved ranged from 40% to 54%, with an acceptable safety profile, mainly including cytokine release syndrome (CRS) and neurotoxicity.
In subsequent years, the use of CAR-T was extended to other subtypes of lymphoma. The data collected confirm that CAR-T therapies against CD19 provide high efficacy and durable remissions in numerous types of non-Hodgkin lymphoma, including in treatment-resistant patients. Despite the risks of CRS and neurotoxicity, modern supportive care regimens and improvements in CAR design have improved the safety of the therapy.
The conclusions indicate that CAR-T immunotherapy has become a key element in the treatment of lymphoproliferative malignancies, and ongoing research is focused on earlier use of this method, combination therapy with checkpoint inhibitors, and the development of CARs targeting new antigens (CD20, CD22, BCMA).
References
Abramson, J. S., Palomba, M. L., Gordon, L. I., Lunning, M. A., Wang, M., Arnason, J. E., Mehta-Shah, N., Maloney, D. G., Andreadis, C., Sehgal, A. R., Munoz, J., Albertson, T. M., Garcia, J., Shah, B. D., Ghosh, N., Reagan, P. M., Penuel, E., Chavez, J. C., & Jacobson, C. A. (2020). Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. The Lancet, 396(10254), 839–852. https://doi.org/10.1016/S0140-6736(20)31366-0
Ayuk, F., Gagelmann, N., von Tresckow, B., Wulf, G., Rejeski, K., Stelljes, M., Penack, O., Baldus, C. D., Kröger, N., Bethge, W., & Dreger, P. (2023). Real-world outcomes of CAR T-cell therapy in large B-cell lymphoma with central nervous system involvement: The GLA/DRST study. Blood Advances, 7(18), 5316–5319. https://doi.org/10.1182/bloodadvances.2023010336
Dreyling, M., Fowler, N. H., Dickinson, M., Martinez-Lopez, J., Kolstad, A., Butler, J., Ghosh, M., Popplewell, L., Chavez, J. C., Bachy, E., Kato, K., Harigae, H., Kersten, M. J., Andreadis, C., Riedell, P. A., Ho, P. J., Pérez-Simón, J. A., Chen, A. I., Nastoupil, L. J., von Tresckow, B., … Schuster, S. J. (2024). Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update. Blood, 143(17), 1713–1725. https://doi.org/10.1182/blood.2023021567
Gauthier, J., Ahn, K. W., Patel, J., Lian, Q., Badawy, S., Cairo, M. S., Delgado, J., Grover, N., Haverkos, B., de Lima, M., Malone, A., Mussetti, A., Nieto, Y., Pawarode, A., Pearson, L., Solh, M., Sureda, A., Tun, A. M., Wudhikarn, K., Yamshon, S., … Herrera, A. F. (2025). CD19 CAR T-Cell Therapy for Primary Mediastinal Large B-Cell Lymphoma: A CIBMTR Analysis. American journal of hematology, 100(10), 1792–1802. https://doi.org/10.1002/ajh.70033
Gauthier, J., Ahn, K. W., Patel, J., Lian, Q., Badawy, S., Cairo, M. S., Delgado, J., Grover, N., Haverkos, B., de Lima, M., et al. (2025). CD19 CAR T-cell therapy for primary mediastinal large B-cell lymphoma: A CIBMTR analysis. American Journal of Hematology. Advance online publication. https://doi.org/10.1002/ajh.70033
Jacobson, C. A., Chavez, J. C., Sehgal, A. R., William, B. M., Munoz, J., Salles, G., Munshi, P. N., Casulo, C., Maloney, D. G., de Vos, S., Reshef, R., Leslie, L. A., Yakoub-Agha, I., Oluwole, O. O., Fung, H. C. H., Rosenblatt, J., Rossi, J. M., Goyal, L., Plaks, V., Yang, Y., … Neelapu, S. S. (2022). Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. The Lancet. Oncology, 23(1), 91–103. https://doi.org/10.1016/S1470-2045(21)00591-X
Lancet Oncology (2022) — Jacobson CA et al., Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial
Neelapu, S. S., Locke, F. L., Bartlett, N. L., Lekakis, L. J., Miklos, D. B., Jacobson, C. A., Braunschweig, I., Oluwole, O. O., Siddiqi, T., Lin, Y., Timmerman, J. M., Stiff, P. J., Friedberg, J. W., Flinn, I. W., Goy, A., Hill, B. T., Smith, M. R., Deol, A., Farooq, U., McSweeney, P., ... Go, W. Y. (2017). Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. The New England Journal of Medicine, 377(26), 2531–2544. https://doi.org/10.1056/NEJMoa1707447
Schuster, S. J., Bishop, M. R., Tam, C. S., Waller, E. K., Borchmann, P., McGuirk, J. P., Jäger, U., Jaglowski, S., Andreadis, C., Westin, J. R., Fleury, I., Bachanova, V., Foley, S. R., Ho, P. J., Mielke, S., Magenau, J. M., Holte, H., Pantano, S., Pacaud, L. B., Awasthi, R., … JULIET Investigators (2019). Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. The New England journal of medicine, 380(1), 45–56. https://doi.org/10.1056/NEJMoa1804980
Wang, M., Munoz, J., Goy, A., Locke, F. L., Jacobson, C. A., Hill, B. T., Timmerman, J. M., Holmes, H., Jaglowski, S., Flinn, I. W., McSweeney, P. A., Miklos, D. B., Pagel, J. M., Kersten, M. J., Milpied, N., Fung, H., Topp, M. S., Houot, R., Beitinjaneh, A., Peng, W., … Reagan, P. M. (2020). KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma. The New England journal of medicine, 382(14), 1331–1342. https://doi.org/10.1056/NEJMoa1914347
Wang, M., Munoz, J., Goy, A., Locke, F. L., Jacobson, C. A., Hill, B. T., Timmerman, J. M., Holmes, H., Jaglowski, S., Flinn, I. W., McSweeney, P. A., Miklos, D. B., Pagel, J. M., Kersten, M. J., Bouabdallah, K., Khanal, R., Topp, M. S., Houot, R., Beitinjaneh, A., Peng, W., … Reagan, P. M. (2023). Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 41(3), 555–567. https://doi.org/10.1200/JCO.21.02370
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