Treatment of patients with relapsed or refractory diffuse large B-cell lymphoma in the Czech Republic in 2025

Czech version

Authors: F. Folber ¹; R. Pytlík ^2,3
Authors‘ workplace: Interní hematologická a onkologická klinika LF MU a FN Brno ¹; Ústav hematologie a krevní transfuze, 1. interní klinika VFN v Praze ²; Interní hematologická klinika FNKV, Praha ³
Published in: Transfuze Hematol. dnes,31, 2025, No. 4, p. 279-286.
Category: Review/Educational Papers
doi: https://doi.org/10.48095/cctahd202523

Overview

CAR-T lymphocytes have become an integral part of the treatment arsenal for haematological malignancies, including B-non-Hodgkin‘s lymphomas (B-NHL). Currently, we have four registered anti-CD19 products available for the treatment of B-NHL. For the treatment of large B-cell lymphomas (LBCL) and follicular lymphoma (FL), axi-cel, liso-cel, and tisa-cel are available, while brexu-cel is registered for the treatment of mantle cell lymphoma (MCL). Registered indications are mostly for the treatment of 3^rd and subsequent lines, but for LBCL we can use axi-cel and liso-cel already in the second line. The presented work addresses: 1. general selection of suitable patients in terms of age and comorbidities; 2. pre-treatment examinations; 3. estimating the risks of adverse effects; 4. the adverse effects; 5. expected outcomes; 6. decision-making algorithms or elements of decision-making algorithms for each malignancy. In the chapter about LBCL, case report is included. The main aim of the work is to assist clinicians who first diagnose relapsed patients and decide on their referral to specialized centres.

Keywords:

side effects – treatment – indications – CAR-T lymphocytes – B-non-Hodgkin’s lymphomas

Sources

1. Yescarta, Souhrn údajů o přípravku. Státní ústav pro kontrolu léčiv, poslední revize textu 8/2024.

2. Breyanzi, Souhrn údajů o přípravku. Státní ústav pro kontrolu léčiv, poslední revize textu 3/2025.

3. Kymriah, Souhrn údajů o přípravku. Státní ústav pro kontrolu léčiv, poslední revize textu 11/2024.

4. Tecartus, Souhrn údajů o přípravku. Státní ústav pro kontrolu léčiv, poslední revize textu 3/2025.

5. Doporučení pro léčbu CAR-T lymfocyty u pacientů s nehodgkinskými lymfomy. In: Belada D, Trněný M (eds): Diagnostické a léčebné postupy u nemocných s maligními lymfomy, XV. vydání. Kooperativní lymfomová skupina, dostupné online: https: //www.lymphoma.cz/pro-pracovniky-ve-zdravotnictvi/8-lecebna-doporuceni/.

6. Folber F, Pytlík R, Polgárová K, et al. Buněčná terapie –⁠ T-lymfocyty s chimerickým antigenním receptorem (CAR-T). In: Doubek M (ed): Červená kniha –⁠ Léčebné postupy v hematologii. Česká hematologická společnost ČLS JEP, dostupné online: https: //www.hematology.cz/cervena-kniha-lecebne-postupy-v-hematologii/.

7. Hayden PJ, Roddie C, Bader P, et al. Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European society for blood and marrow transplantation (EBMT) and the Joint accreditation committee of ISCT and EBMT (JACIE) and the European haematology association (EHA). Ann Oncol. 2022; 33 (3): 259–275.

8. Rejeski K, Perez A, Sesques P, et al. CAR-HEMATOTOX: a model for CAR T-cell–related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Blood. 2021; 138 (24): 2499–2513.

9. Rejeski K, Wang Y, Albanyan O, et al. The CAR-HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL. Am J Hematol. 2023; 98 (11): 1699–1710.

10. Sesques P, Kirkwood AA, Kwon M, et al. Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma. J Hematol Oncol. 2024; 6; 17 (1): 61.

11. Joseph T, Sanchez J, Abbasi A, et al. Cardiotoxic effects following CAR-T cell therapy: a literature review. Curr Oncol Rep. 2025; 27 (2): 135–147.

12. Pudil R, Danzig V, Veselý J, et al. Doporučené postupy Evropské kardiologické společnosti pro kardioonkologii z roku 2022 vypracované ve spolupráci s European Hematology Association (EHA), European Society for Therapeutic Radiology and Oncology (ESTRO) a International Cardio-Oncology Society (IC-OS). Lyon AR, López-Fernández T, Couch LS, et al; ESC Scientific Document Group. Překlad zkráceného dokumentu připravený Českou kardiologickou společností. Cor Vasa. 2023; 65 : 350–434.

13. Yamshon S, Gribbin C, Alhomoud M. Safety and toxicity profiles of CAR T cell therapy in non-Hodgkin lymphoma: a systematic review and meta-analysis. Clin Lymphoma Myeloma Leuk. 2024; 24 (6): e235–e256.e2.

14. 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): 625–638.

15. Jacobson CA, Munoz J, Sun F, et al. Real-world outcomes with chimeric antigen receptor T cell therapies in large B cell lymphoma: a systematic review and meta-analysis. Transplant Cell Ther. 2024; 30 (1): 77.e1–77.e15.

16. Jain MD, Smith M, Shah NN. How I treat refractory CRS and ICANS after CAR T-cell therapy. Blood. 2023; 141 (20): 2430–2442.

17. Park JH, Nath K, Devlin SM, et al. CD19 CAR T-cell therapy and prophylactic anakinra in relapsed or refractory lymphoma: phase 2 trial interim results. Nat Med. 2023; 29 (7): 1710–1717.

18. Rejeski K, Subklewe M, Aljurf M, et al. Immune effector cell-associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations. Blood. 2023; 142 (10): 865–877.

19. Cordas dos Santos DM, Tix T, Shouval R, et al. A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy. Nat Med. 2024; 30 (9): 2667–2678.

20. Shahid Z, Jain T, Dioverti V, et al. Best practice considerations by the American society of transplant and cellular therapy: infection prevention and management after chimeric antigen receptor T cell therapy for hematological malignancies. Transplant Cell Ther. 2024; 30 (10): 955–969.

21. Reynolds G, Hall VG, Teh BW. Vaccine schedule recommendations and updates for patients with hematologic malignancy post-hematopoietic cell transplant or CAR T-cell therapy. Transpl Infect Dis. 2023; 25 (Suppl 1): e14109.

22. Steiner RE, Banchs J, Koutroumpakis E, et al. Cardiovascular events in patients treated with chimeric antigen receptor T-cell therapy for aggressive B-cell lymphoma. Haematologica. 2022; 107 (7): 1555–1566.

23. Gutierrez C, Neilan TG, Grover NS. How I approach optimization of patients at risk of cardiac and pulmonary complications after CAR T-cell therapy. Blood. 2023; 141 (20): 2452–2459.

24. Elsallab M, Ellithi M, Lunning MA, et al. Second primary malignancies after commercial CAR T-cell therapy: analysis of the FDA adverse events reporting system. Blood. 2024; 143 (20): 2099–2105.

25. Hu J, Dunbar CE. T-cell lymphomas in recipients of CAR-T cells: assessing risks and causalities. Blood. 2024; 144 (24): 2473–2481

26. 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.

27. 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): 2531–2544.

28. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020; 396 (10254): 839–852.

29. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022; 386 (7): 640–654.

30. Abramson JS, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study. Blood. 2023; 141 (14): 1675–1684.

31. 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): 2145–2154.

32. Jain MD, Jacobs MT, Gao F, et al. Bridging therapy with axicabtagene ciloleucel for large B-cell lymphoma: results from the US Lymphoma CAR-T Consortium. Blood Adv. 2024; 8 (4): 1042–1050.

33. Iacoboni G, Sánchez-Salinas MA, et al. Efficacy and safety of bendamustine-containing bridging therapy in R/R LBCL patients receiving CD19 CAR T-cells. Hemasphere. 2024; 8 (7): e86.

34. Alhomoud M, Ibrahim R, Demetres M, et al. Safety and efficacy of bridging radiation therapy prior to CD19 CAR T for non-Hodgkin lymphoma: a systematic review and meta-analysis. Haematologica. 2025 Jul 10. Online ahead of print. DOI: 10.3324/haematol.2025. 287547.

35. 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): 325–332.

36. Jacobson CA, Chavez JC, Sehgal AR, et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022; 23 (1): 91–103.

37. Morschhauser F, Dahiya S, Palomba ML, et al. Lisocabtagene maraleucel in follicular lymphoma: the phase 2 TRANSCEND FL study. Nat Med. 2024; 30 (8): 2199–2207.

38. Dickinson M, Martinez-Lopez J, Jousseaume E, et al. Comparative efficacy and safety of tisagenlecleucel and axicabtagene ciloleucel among adults with r/r follicular lymphoma. Leuk Lymphoma. 2024; 65 (3): 323–332.

39. Ghione P, Palomba ML, Patel AR, et al. Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma. Blood. 2022; 140 (8): 851–860.

40. Salles G, Schuster SJ, Dreyling M, et al. Efficacy comparison of tisagenlecleucel vs usual care in patients with relapsed or refractory follicular lymphoma. Blood Adv. 2022; 6 (22): 5835–5843.

41. Nastoupil LJ, Bonner A, Wang P, et al. Matching-adjusted indirect comparison of efficacy and safety of lisocabtagene maraleucel and mosunetuzumab for the treatment of third-line or later relapsed or refractory follicular lymphoma. Exp Hematol Oncol. 2025; 14 (1): 30.

42. Iqbal M, Kumar A, Dreger P, et al. Clinical practice recommendations for hematopoietic cell transplantation and cellular therapies in follicular lymphoma: a collaborative effort on behalf of the American Society for Transplantation and Cellular Therapy and the European Society for Blood and Marrow Transplantation. Transplant Cell Ther. 2024; 30 (9): 832–843.

43. Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022; 23 (8): 1055–1065.

44. Linton KM, Vitolo U, Jurczak W, et al. Epcoritamab monotherapy in patients with relapsed or refractory follicular lymphoma (EPCORE NHL-1): a phase 2 cohort of a single-arm, multicentre study. Lancet Haematol. 2024; 11 (8): e593–e605.

45. Kim TM, Taszner M, Novelli S, et al. Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma. Ann Oncol. 2024; 35 (11): 1039–1047.

46. Russler-Germain DA, Bartlett NL. Sequencing bispecific antibodies and CAR T cells for FL. Hematology Am Soc Hematol Educ Program. 2024; 2024 (1): 310–317.

47. Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-Cell Therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020; 382 (14): 1331–1342.

48. Ahmed N, Thiruvengadam S, Hamadani M, et al. Real-world outcomes of brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma: a CIBMTR analysis. Blood Adv. 2025 Jul 24: Online ahead of print. DOI: bloodadvances.2024015014.

49. Hess G, Dreyling M, Oberic L, et al. Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma. Leuk Lymphoma. 2024; 65 (1): 14–25.

50. Salles G, Chen JMH, Zhang I, et al. Matching-adjusted indirect comparison of brexucabtagene autoleucel (ZUMA-2) and pirtobrutinib (BRUIN) in patients with relapsed/refractory mantle cell lymphoma previously treated with a covalent bruton tyrosine kinase inhibitor. Adv Ther. 2024; 41 (5): 1938–1952.

51. Phillips TJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab in relapsed/refractory mantle cell lymphoma: results from a phase I/II study. J Clin Oncol. 2025; 43 (3): 318–328.

52. McCulloch R, Visco C, Eyre TA, et al. Efficacy of R-BAC in relapsed, refractory mantle cell lymphoma post BTK inhibitor therapy. Br J Haematol. 2020; 189 (4): 684–688.

53. Dreyling M, Doorduijn J, Giné E, et al. Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network. Lancet. 2024; 403 (10441): 2293–2306.

54. Wang M, Salek D, Belada D, et al. ECHO Investigators. Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma. J Clin Oncol. 2025; 43 (20): 2276–2284.