O uso do Brexucabtagene Autoleucel no tratamento de Linfoma de Células do Manto em pacientes Recidivados/refratários
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Jun 13, 2025
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Objetivo: Descrever as evidências científicas que favorecem o uso da terapia com células T (CAR-T) no tratamento do Linfoma de Células do Manto recidivado/refratário (LCM R/R). Métodos: A pesquisa foi realizada em bases científicas (PubMed, SciELO, BVS) entre dezembro/2024 e fevereiro/2025, usando os descritores "Hematology”, “Mantle-Cell Lymphoma”, “brexucabtagene autoleucel”, “CAR-T Cell” no MeSH. Incluiu artigos gratuitos em inglês, português ou espanhol, publicados nos últimos 05 anos. Resultados: O LCM é um subtipo raro e agressivo de Linfoma Não Hodgkin, associado a mutações genéticas ativadoras da ciclina D1 com a promoção da proliferação celular. O diagnóstico envolve biópsias de tecidos, análise com anatomopatológico e imunohistoquímica, além da complementação com exames genéticos. O tratamento com brexucabtagene autoleucel (KTE-X19), (um subtipo de terapia com células CAR-T) em pacientes com LCM R/R é uma terapia inovadora, com alta eficácia. Esta revisão integrativa analisou estudos recentes sobre o KTE-X19, avaliando suas respostas terapêuticas, riscos e prognóstico. Considerações finais: O uso do brexucabtagene autoleucel apresenta bons índices de respostas mesmo em pacientes refratários ou recidivados. Apresenta boa segurança e bom manejo clínico de efeitos adversos, associado a um melhor custo-benefício, quando comparado com outros medicamentos disponíveis nesta linha de terapia no momento.
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SantosD. O., CalasansH. C. M., MarquesM. de O., PradoA. B. L. F., CarvalhoA. L. M. F. de, SantosA. E. O. dos, JesusY. H. A. de, MeloB. S., SantanaK. L., & AndradeJ. P. F. (2025). O uso do Brexucabtagene Autoleucel no tratamento de Linfoma de Células do Manto em pacientes Recidivados/refratários. Revista Eletrônica Acervo Saúde, 25(6), e20837. https://doi.org/10.25248/reas.e20837.2025
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Referências
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14. HUANG Z, et al. CAR T-Cell therapy for the management of mantle cell lymphoma. Molecular Cancer, 2023; 22(1): 67.
15. IACOBONI G, et al. Real-world evidence of brexucabtagene autoleucel for the treatment of relapsed or refractory mantle cell lymphoma. Blood advances, 2022; 6(12): 3606-3610.
16. JAIN P e WANG M. Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management. Am J Hematology, 2019; 94: 710–25.
17. JAIN P e WANG ML. Mantle cell lymphoma in 2022: A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments. Am J Hematol, 2022; 97: 638–56.
18. KUMAR A, et al. New directions for mantle cell lymphoma in 2022. American Society of Clinical Oncology Educational Book, 2022; 42: 614-628.
19. LI S, et al. The pathologic diagnosis of mantle cell lymphoma, 2021.
20. MALARIKOVA D, et al. Concurrent TP53 and CDKN2A gene aberrations in newly diagnosed mantle cell lymphoma correlate with chemoresistance and call for innovative upfront therapy. Cancers, 2020; 12: 2120.
21. MASSARO F, et al. Long‐term results of the MCL01 phase II trial of rituximab plus HyperCVAD alternating with high‐dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma. British Journal of Haematology, 2021; 192(6): 1011-1014.
22. MENARDI G. et al. Management of chimeric antigen receptor T-cell-related toxicity of a patient affected by cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, followed by an intestinal perforation: a case report. Journal of Medical Case Reports, 2025; 19(1): 2025.
23. MERRYMAN RW, et al. Rituximab/bendamustine and rituximab/cytarabine induction therapy for transplant-eligible mantle cell lymphoma. Blood, 2020; 4: 858–67.
24. MIAN A e HILL BT. Brexucabtagene autoleucel for the treatment of relapsed/refractory mantle cell lymphoma. Expert opinion on biological therapy, 2021; 21(94): 435-441.
25. NIE EH, et al. Clinical features of neurotoxicity after CD19 CAR T-cell therapy in mantle cell lymphoma. Blood Advances, 2024; 8(6): 1474-1486.
26. PETERSOHN S, et al. Cost-effectiveness analysis of KTE-X19 CAR T therapy versus real-world standard of care in patients with relapsed/refractory mantle cell lymphoma post BTKi in England. Journal of Medical Economics, 2022; 25(1): 730-740.
27. PICANO-CASTRO V, et al. Emerging CAR T cell therapies: clinical landscape and patent technological routes. Human vaccines & immunotherapeutics, 2020; 16(6): 1424-1433.
28. RADHAKRISHNAN VS, et al. Mantle cell lymphoma: A clinical review of the changing treatment paradigms with the advent of novel therapies, and an insight into Indian data. Cancer Rep. 2022; 5: 1590.
29. REJESKI K 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. American journal of hematology, 2023; 98(11): 1699-1710.
30. ROMAGUERA JE, et al. Frequency of gastrointestinal involvement and its clinical significance in mantle cell lymphoma. Cancer, 2003; 97: 586–91.
31. ROSENWALD A, et al. The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell, 2003; 3: 185–197.
32. RUAN J. Molecular pro ling and management of mantle cell lymphoma. Hematology Am Soc Hematol Educ Program, 2019; 30–40.
33. SADEGHI L e WRIGHT AP. Migration and adhesion of B-Lymphocytes to specific microenvironments in mantle cell lymphoma: interplay between signaling pathways and the epigenetic landscape. Int J Mol Sci, 2021; 22: 6247.
34. SIMONS CL, et al. Cost-effectiveness for KTE-X19 CAR T therapy for adult patients with relapsed/refractory mantle cell lymphoma in the United States. Journal of Medical Economics, 2021; 24(1): 421-431.
35. SONG Y, et al. Safety and activity of the investigational bruton tyrosine kinase inhibitor zanubrutinib (BGB-3111) in patients with mantle cell lymphoma from a phase 2 trial. Blood, 2018; 132(1): 148.
36. STELLA F, et al. Brexucabtagene autoleucel in‐vivo expansion and BTKi refractoriness have a negative influence on progression‐free survival in mantle cell lymphoma: Results from CART‐SIE study. British Journal of Haematology, 2025.
37. SWERDLOW SH, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood, The Journal of the American Society of Hematology, 2016; 127(20): 2375-2390.
38. SZCZEŚNIAK M, et al. Autologous stem cell transplantation for mantle cell lymphoma single centre experience. Contemp Oncol (Pozn), 2013; 17: 456–9.
39. TAM CS, et al. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med, 2018; 378(13): 1211–1223.
40. VOORDECKERS LB, et al. Imunoterapia com células CAR-T como nova perspectiva de tratamento das neoplasias hematológicas. Brazilian Journal of Health Review, 2024; 7(1): 2666-2678.
41. WANG M, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet, 2018; 391(10121): 659–667.
42. WANG M, et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med, 2020; 382(14): 1331–1342.
43. WANG M, et al. 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, 2022.
44. WANG ML, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013; 369(6): 507–516.
45. WANG Y, et al. Brexucabtagene autoleucel for relapsed/refractory mantle cell lymphoma: real world experience from the US lymphoma CAR T consortium. Blood, 2021; 138: 744.
2. ARMITAGE JO e LONGO DL. Mantle-Cell Lymphoma. Hardin CC, editor. Massachusetts Medical Society, 2022; 386: 2495–506.
3. BEEKMAN R, et al. SOX11, a key oncogenic factor in mantle cell lymphoma. Curr Opin Hematol, 2018; 25: 299–306.
4. DREYLING M, et al. Newly diagnosed and relapsed mantle cell lymphoma: ESMO clinical practice guidelines for diagnosis, treatment and follow‐up. Ann Oncol, 2017; 28(4): 62‐71.
5. FU K, et al. Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling. Blood, 2005; 106: 4315–21.
6. GAO D e LIU Z. Cyclin D1 + large B-cell lymphoma with altered CCND1 and BCL-6 rearrangements: a diagnostic challenge. Biomarker research. England, 2019; 7: 11.
7. GEISLER CH, et al. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo–purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood, 2008; 112: 2687–93.
8. HAMILTON MP, et al. CAR19 monitoring by peripheral blood immunophenotyping reveals histology-specific expansion and toxicity. Blood Advances, 2024; 8(12): 3314-3326.
9. HANEL W e EPPERLA N. Emerging therapies in mantle cell lymphoma. J Hematol Oncol, 2020; 13: 79.
10. HERMINE O, et al. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma N. The Lancet Elsevier, 2016; 388: 565–75.
11. HESS G, et al. Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma. Leukemia & Lymphoma, 2024; 45(1): 14-25.
12. HOSEIN PJ, et al. Updated survival analysis of two sequential prospective trials of R-MACLO-IVAM followed by maintenance for newly diagnosed mantle cell lymphoma. American Journal of Hematology. John Wiley & Sons, Ltd, 2015; 90: 111–6.
13. HOSTER E, et al. Prognostic value of ki-67 index, cytology, and growth pattern in mantle-cell lymphoma: results from randomized trials of the european mantle cell lymphoma network. J Clin Oncol, 2016; 34: 1386–95.
14. HUANG Z, et al. CAR T-Cell therapy for the management of mantle cell lymphoma. Molecular Cancer, 2023; 22(1): 67.
15. IACOBONI G, et al. Real-world evidence of brexucabtagene autoleucel for the treatment of relapsed or refractory mantle cell lymphoma. Blood advances, 2022; 6(12): 3606-3610.
16. JAIN P e WANG M. Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management. Am J Hematology, 2019; 94: 710–25.
17. JAIN P e WANG ML. Mantle cell lymphoma in 2022: A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments. Am J Hematol, 2022; 97: 638–56.
18. KUMAR A, et al. New directions for mantle cell lymphoma in 2022. American Society of Clinical Oncology Educational Book, 2022; 42: 614-628.
19. LI S, et al. The pathologic diagnosis of mantle cell lymphoma, 2021.
20. MALARIKOVA D, et al. Concurrent TP53 and CDKN2A gene aberrations in newly diagnosed mantle cell lymphoma correlate with chemoresistance and call for innovative upfront therapy. Cancers, 2020; 12: 2120.
21. MASSARO F, et al. Long‐term results of the MCL01 phase II trial of rituximab plus HyperCVAD alternating with high‐dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma. British Journal of Haematology, 2021; 192(6): 1011-1014.
22. MENARDI G. et al. Management of chimeric antigen receptor T-cell-related toxicity of a patient affected by cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, followed by an intestinal perforation: a case report. Journal of Medical Case Reports, 2025; 19(1): 2025.
23. MERRYMAN RW, et al. Rituximab/bendamustine and rituximab/cytarabine induction therapy for transplant-eligible mantle cell lymphoma. Blood, 2020; 4: 858–67.
24. MIAN A e HILL BT. Brexucabtagene autoleucel for the treatment of relapsed/refractory mantle cell lymphoma. Expert opinion on biological therapy, 2021; 21(94): 435-441.
25. NIE EH, et al. Clinical features of neurotoxicity after CD19 CAR T-cell therapy in mantle cell lymphoma. Blood Advances, 2024; 8(6): 1474-1486.
26. PETERSOHN S, et al. Cost-effectiveness analysis of KTE-X19 CAR T therapy versus real-world standard of care in patients with relapsed/refractory mantle cell lymphoma post BTKi in England. Journal of Medical Economics, 2022; 25(1): 730-740.
27. PICANO-CASTRO V, et al. Emerging CAR T cell therapies: clinical landscape and patent technological routes. Human vaccines & immunotherapeutics, 2020; 16(6): 1424-1433.
28. RADHAKRISHNAN VS, et al. Mantle cell lymphoma: A clinical review of the changing treatment paradigms with the advent of novel therapies, and an insight into Indian data. Cancer Rep. 2022; 5: 1590.
29. REJESKI K 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. American journal of hematology, 2023; 98(11): 1699-1710.
30. ROMAGUERA JE, et al. Frequency of gastrointestinal involvement and its clinical significance in mantle cell lymphoma. Cancer, 2003; 97: 586–91.
31. ROSENWALD A, et al. The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell, 2003; 3: 185–197.
32. RUAN J. Molecular pro ling and management of mantle cell lymphoma. Hematology Am Soc Hematol Educ Program, 2019; 30–40.
33. SADEGHI L e WRIGHT AP. Migration and adhesion of B-Lymphocytes to specific microenvironments in mantle cell lymphoma: interplay between signaling pathways and the epigenetic landscape. Int J Mol Sci, 2021; 22: 6247.
34. SIMONS CL, et al. Cost-effectiveness for KTE-X19 CAR T therapy for adult patients with relapsed/refractory mantle cell lymphoma in the United States. Journal of Medical Economics, 2021; 24(1): 421-431.
35. SONG Y, et al. Safety and activity of the investigational bruton tyrosine kinase inhibitor zanubrutinib (BGB-3111) in patients with mantle cell lymphoma from a phase 2 trial. Blood, 2018; 132(1): 148.
36. STELLA F, et al. Brexucabtagene autoleucel in‐vivo expansion and BTKi refractoriness have a negative influence on progression‐free survival in mantle cell lymphoma: Results from CART‐SIE study. British Journal of Haematology, 2025.
37. SWERDLOW SH, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood, The Journal of the American Society of Hematology, 2016; 127(20): 2375-2390.
38. SZCZEŚNIAK M, et al. Autologous stem cell transplantation for mantle cell lymphoma single centre experience. Contemp Oncol (Pozn), 2013; 17: 456–9.
39. TAM CS, et al. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med, 2018; 378(13): 1211–1223.
40. VOORDECKERS LB, et al. Imunoterapia com células CAR-T como nova perspectiva de tratamento das neoplasias hematológicas. Brazilian Journal of Health Review, 2024; 7(1): 2666-2678.
41. WANG M, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet, 2018; 391(10121): 659–667.
42. WANG M, et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med, 2020; 382(14): 1331–1342.
43. WANG M, et al. 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, 2022.
44. WANG ML, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013; 369(6): 507–516.
45. WANG Y, et al. Brexucabtagene autoleucel for relapsed/refractory mantle cell lymphoma: real world experience from the US lymphoma CAR T consortium. Blood, 2021; 138: 744.