CAR-T Cell Therapy in Real-World Clinical Practice: An Experience of the NN Alexandrov National Cancer Centre of Belarus

N.E. Konoplya, Volha Aleksandrovna Kalenik, P.D. Dziameshka, E.Yu. Zharkova, T.V. Savich, T.M. Doroshenko, I.N. Seviaryn, N.M. Bobrova, A.A. Beleevsky, E.Kh. Sarydze, S.L. Polyakov,

DOI:

https://doi.org/10.21320/2500-2139-2025-18-4-305-314

BACKGROUND. The therapy using T-cells with chimeric antigen receptor (CAR) is a novel and effective treatment option for relapsed/refractory B-cell non-Hodgkin lymphomas (r/r В-NHL). However, high cost of commercial products limits their application in real-world clinical practice. Academic approach to manufacturing CAR-T cell products can reduce the costs and improve availability and affordability of this therapy option.

AIM. To assess the efficacy and safety of the use of academic CAR-T cell products in r/r В-NHL patients.

MATERIALS & METHODS. From June 2021 to November 2024, this prospective study enrolled 57 r/r В-NHL patients treated at the NN Alexandrov National Cancer Centre of Belarus (Minsk, Republic of Belarus). The patients were 23–68 years of age (median 47 years), there were 32 men and 25 women. The CAR-T cell product was manufactured using lentiviral vector encoding anti-CD19 CAR.

RESULTS. Generally, complete response was achieved in 37 (64.9 %) out of 57 patients. The 3-year overall survival (OS) was 63 ± 8 % (median not reached). Among patients with follicular lymphoma, complete response was achieved in 12/15 patients (80 %). The 3-year OS was 93 ± 6 %. The safety profile was acceptable: cytokine release syndrome was detected in 38.6 % of patients (predominantly grade 1–2), and neurotoxicity (ICANS) was identified in 31.6 % of patients.

CONCLUSION. In r/r В-NHL treatment, academic CAR-T cell products show comparable efficacy and safety to their commercial counterparts. Their use can considerably decrease the cost and increase availability and affordability of this novel therapy option for more people.

  1. 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(26):2531–44. doi: 10.1056/NEJMoa1707447. DOI: https://doi.org/10.1056/NEJMoa1707447
  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(1):45–56. doi: 10.1056/NEJMoa1804980. DOI: https://doi.org/10.1056/NEJMoa1804980
  3. 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(1):31–42. doi: 10.1016/S1470-2045(18)30864-7. DOI: https://doi.org/10.1016/S1470-2045(18)30864-7
  4. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396(10254):839–52. doi: 10.1016/S0140-6736(20)31366-0. DOI: https://doi.org/10.1016/S0140-6736(20)31366-0
  5. Parker C, Liu FF, Deger KA, et al. Cost-effectiveness of lisocabtagene maraleucel versus axicabtagene ciloleucel and tisagenlecleucel in the third-line or later treatment setting for relapsed or refractory large B-cell lymphoma in the United States. Adv Ther. 2023;40(5):2355–74. doi: 10.1007/s12325-023-02444-x. DOI: https://doi.org/10.1007/s12325-023-02444-x
  6. Levine BL, Miskin J, Wonnacott K, et al. Global manufacturing of CAR T cell therapy. Mol Ther Methods Clin Dev. 2017;4:92–101. doi: 10.1016/j.omtm.2016.12.006. DOI: https://doi.org/10.1016/j.omtm.2016.12.006
  7. Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25(4):625–38. doi: 10.1016/j.bbmt.2018.12.758. DOI: https://doi.org/10.1016/j.bbmt.2018.12.758
  8. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800–8. doi: 10.1182/blood-2017-03-769620. DOI: https://doi.org/10.1182/blood-2017-03-769620
  9. Park JH, Rivière I, Gonen M, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378(5):449–59. doi: 10.1056/NEJMoa1709919. DOI: https://doi.org/10.1056/NEJMoa1709919
  10. NCCN Guidelines Version 2.2025. B-Cell Lymphomas. Available from: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480 (accessed 17.06.2025).
  11. Bachy E, Le Gouill S, Di Blasi R, et al. A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma. Nat Med. 2022;28(10):2145–54. doi: 10.1038/s41591-022-01969-y. DOI: https://doi.org/10.1038/s41591-022-01969-y
  12. Neelapu SS, Chavez JC, Sehgal AR, et al. Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5). Blood. 2024;143(6):496–506. doi: 10.1182/blood.2023021243. DOI: https://doi.org/10.1182/blood.2023021243
  13. Fowler NH, Dickinson M, Dreyling M, et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nat Med. 2022;28(2):325–32. doi: 10.1038/s41591-021-01622-0. DOI: https://doi.org/10.1038/s41591-021-01622-0
  14. Ruella M, Kenderian SS, Shestova O, et al. The addition of the BTK inhibitor ibrutinib to anti-CD19 chimeric antigen receptor T cells (CART19) improves responses against mantle cell lymphoma. Clin Cancer Res. 2016;22(11):2684–96. doi: 10.1158/1078-0432.CCR-15-1527. DOI: https://doi.org/10.1158/1078-0432.CCR-15-1527
  15. Brentjens RJ, Davila ML, Riviere I, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013;5(177):177ra38. doi: 10.1126/scitranslmed.3005930. DOI: https://doi.org/10.1126/scitranslmed.3005930
  16. Zah E, Lin MY, Silva-Benedict A, et al. T cells expressing CD19/CD20 bispecific chimeric antigen receptors prevent antigen escape by malignant B cells. Cancer Immunol Res. 2016;4(6):498–508. doi: 10.1158/2326-6066.CIR-15-0231. DOI: https://doi.org/10.1158/2326-6066.CIR-15-0231
  17. Hong M, Clubb JD, Chen YY. Engineering CAR-T Cells for Next-Generation Cancer Therapy. Cancer Cell. 2020;38(4):473–88. doi: 10.1016/j.ccell.2020.07.005. DOI: https://doi.org/10.1016/j.ccell.2020.07.005
  18. Jacobson CA, Locke FL, Ma L, et al. Real-World Evidence of Axicabtagene Ciloleucel for the Treatment of Large B Cell Lymphoma in the United States. Transplant Cell Ther. 2022;28(9):581.e1–581.e8. doi: 10.1016/j.jtct.2022.05.026. DOI: https://doi.org/10.1016/j.jtct.2022.05.026
  19. Locke FL, Rossi JM, Neelapu SS, et al. Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma. Blood Adv. 2020;4(19):4898–911. doi: 10.1182/bloodadvances.2020002394. DOI: https://doi.org/10.1182/bloodadvances.2020002394

Keywords:

academic CAR-T cell products, B-cell non-Hodgkin lymphomas, efficacy, safety

License

Copyright (c) 2025 Clinical Oncohematology. Basic Research and Clinical Practice

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Downloads

Download data is not yet available.

For Contact

  • Volha Aleksandrovna Kalenik, канд. мед. наук, NN Alexandrov National Cancer Centre of Belarus, Lesnoi ag., Minsk, Republic of Belarus, 223040, e-mail: olga.a.kalenik@mail.ru

Downloads

Published

01.10.2025

Issue

Vol. 18 No. 4 (2025)
LYMPHOID TUMORS

How to Cite

Konoplya N.E., Kalenik V.A., Dziameshka P.D., et al. CAR-T Cell Therapy in Real-World Clinical Practice: An Experience of the NN Alexandrov National Cancer Centre of Belarus. Clinical Oncohematology. Basic Research and Clinical Practice. 2025;18(4):305–314. doi:10.21320/2500-2139-2025-18-4-305-314.