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DOI: 10.5935/2526-8732.20240443
Use of CAR-T cells for the treatment of relapsed and refractory multiple myeloma: a systematic review
Uso de células CAR-T no tratamento de mieloma múltiple recidivado e refratário: uma revisão sistemática Financial support: none to declare.ABSTRACT
A systematic review of published articles based on randomized clinical trials was conducted to ascertain the efficacy or perspective of using CAR-T cell therapy for refractory multiple myeloma. The PubMed database was searched with the combination of terms “multiple myeloma”, “refractory multiple myeloma”, “CAR T-cell”, and the PRISMA criteria were followed. Of the 78 articles found, only 5 were selected. The studies used different treatment protocols and four different types of CAR-T cells. All studies obtained interesting results in terms of increased progression-free survival and negative minimal residual disease responses. Some authors detected an expansion of CAR-T cells and noted dose-dependent relationship between treatment effectiveness and serum BCMA levels. Although the results were promising, a small number of patients still relapsed a few months after CAR-T cell infusion. Therefore, this new line of therapy should be further investigated, as it significantly increases progression-free survival and improves quality of life.
RESUMO
Uma revisão sistemática de artigos publicados com base em ensaios clínicos randomizados foi realizada para verificar a eficácia ou perspectiva do uso da terapia com células CAR-T para mieloma múltiplo refratário. Foi pesquisada a base de dados PubMed com a combinação dos termos “multiple myeloma”, “refratory multiple myeloma”, “CAR T-cell” e foram seguidos os critérios PRISMA. Dos 78 artigos encontrados, apenas 5 foram selecionados. Os estudos utilizaram diferentes protocolos de tratamento e quatro tipos diferentes de células CAR-T. Todos os estudos obtiveram resultados interessantes em termos de aumento da sobrevida livre de progressão e respostas negativas à doença residual mínima. Alguns autores detectaram uma expansão das células CAR-T e observaram uma relação dose-dependente entre a eficácia do tratamento e os níveis séricos de BCMA. Embora os resultados tenham sido promissores, um pequeno número de pacientes ainda apresentou recaída alguns meses após a infusão de células CAR-T. Portanto, esta nova linha de terapia deve ser mais investigada, pois aumenta significativamente a sobrevida livre de progressão e melhora a qualidade de vida.
Descritores:
Mieloma múltiplo - Imunoterapia adotiva - Antígeno de maturação de células B - RecorrênciaPublikationsverlauf
Eingereicht: 21. Dezember 2023
Angenommen: 25. Januar 2024
Artikel online veröffentlicht:
25. Januar 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)
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Satchie Sakamoto, Vanessa Sgnaolin. Use of CAR-T cells for the treatment of relapsed and refractory multiple myeloma: a systematic review. Brazilian Journal of Oncology 2024; 20: e-20240443.
DOI: 10.5935/2526-8732.20240443
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REFERENCES
- 1 Rajkumar SV. Multiple myeloma: 2018 update on diagnosis, risk-stratification and management. Am J Hematol 2019; 93 (08) 981-1114
- 2 Ria R, Vacca A. Bone marrow stromal cells-induced drug resistance in multiple myeloma. Int J Mol Sci 2020; 21 (02) 613
- 3 Tang F, Lu Y, Ge Y, Shang J, Zhu X. Infusion of chimeric antigen receptor T-cells against dual targets of CD19 and B cell maturation antigen for the treatment of refractory Multiple Myeloma. J Int Med Res 2020; Jan 48 (01) 1-7
- 4 Rajkumar SV, Kumar S. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc 2016; 91 (01) 101-19
- 5 Pinto V, Bergantim R, Caires HR, Seca H, Guimarães J, Vasconcelos MH. Multiple myeloma: available therapies and causes of drug resistance. Cancers 2020; 12 (02) 407
- 6 Roshal M. Minimal residual disease detection by flow cytometry in multiple myeloma: why and how?. Semin Hematol 2018; Jan 55 (01) 4-12
- 7 Zhao WH, Liu J, Wang BY, Chen YX, Cao XM, Yang Y. et al. A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. J Hematol Oncol 2018; Dec 11 (01) 141
- 8 Lee J, Kim SH. Treatment of relapsed and refractory multiple myeloma. Blood Res 2020; Jul 55 Suppl 1 S43-S53
- 9 Chim CS, Kumar SK, Orlowski RZ, Richardson PG, Gertz MA, Giralt S. et al. Management of relapsed and refractory Multiple Myeloma: novel agents, antibodies, immunotherapies and beyond. Leukemia 2018; Feb 32 (02) 252-62
- 10 Xu J, Chen LJ, Yang SS, Sun Y, Wu W, Liu YF. et al. Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen on relapsed/refractory multiple myeloma. PNAS license 2019; 116 (19) 9543-51
- 11 Maples KT, Joseph NS, Harvey RD. Current developments in the combination therapy of relapsed/refractory multiple myeloma. Expert Rev Anticancer Ther 2020; Sep 20 (12) 1021-35
- 12 Dempsey JL, Johns A, Rosko AE, Lazarus HM. The pharmacologic management of multiple myeloma in older adults. Expert Opin Pharmacother 2019; May 20 (07) 887-902
- 13 Petty AJ, Heyman B, Yang Y. Chimeric antigen receptor cell therapy: overcoming obstacle to battle cancer. Cancers 2020; Mar 12 (04) 842
- 14 Zhang Q, Ping J, Huang Z, Zhang X, Zhou J, Wang G. et al. CAR T-cell therapy in cancer: tribulations and road ahead. J Immunol Res 2020; Jan 2020: 1924379
- 15 Huang H, Wu HW, Hu YX. Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma. J Zhejiang Univ Sci B 2020; 21 (01) 29-41
- 16 Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D. et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med 2019; May 380 (18) 1726-37
- 17 Brudno JN, Maric I, Hartman SD, Rose JJ, Wang M, Lam N. et al. T cells genetically modified to express an anti B cell maturation antigen chimeric antigen receptor causes remissions of poor prognosis relapsed Multiple Myeloma. J Clin Oncol 2018; Aug 36 (22) 2267-79
- 18 Moher D, Liberati A, Tetzlaff J, Altman DG. The PRISMA Group. Preferred reporting items for systemic review and meta-analyses: the PRISMA statement. PLoS Med 2009; Jul 6 (07) e1000097
- 19 Barbosa TF, Lira AB, Neto OBO, Santos LL, Santos IO, Barbosa LT. et al. Tutorial para execução de revisões sistemáticas e metanálises com estudos de intervenção em anestesia. Rev Bras Anestesiol 2018; May/Jun 69 (03) 299-306
- 20 Higgins JP, Altman DG, Gotzsche PC, Jüni P, Moher D, Oxman AD. et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928
- 21 Yan Z, Cao J, Cheng H, Qiao J, Zhang H, Wang Y. et al. A combination of humanized anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase 2 trial. Lancet Haematol 2019; Oct 6 (10) E521-E9
- 22 U.S. Department of Health and Human Service (US), National Institutes of Health (NIH), National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0 [internet]. Washington: U.S. Department of Health and Human Service; 2009. May; [access in 2023 Dec 09]. Available from https://www.eortc.be/services/doc/ctc/ctcae_4.03_2010-06-14_quickreference_5x7.pdf
- 23 Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M. et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 2014; Jul 124 (02) 188-95
- 24 Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL. et al. Chimeric antigen receptor T-cell therapy – assessment and management of toxicities. Nat Rev Clin Oncol 2018; Jan 15 (01) 47-62
- 25 Cho SF, Anderson KC, Tai YT. Targeting B cell maturation antigen (BCMA) in multiple myeloma: potential uses of BCMA-based immunotherapy. Front Immunol 2018; 9: 1821
- 26 Cohen AD, Garfall AL, Stadmauer EA, Melenhorst JJ, Lacey SF, Lancaster E. et al. B cell maturation antigenspecific CAR T cells are clinically active in multiple myeloma. J Clin Invest 2019; Mar 129 (06) 2210-21
- 27 Caraccio C, Krishna S, Philips DJ, Schürch CM. Bispecific antibodies for multiple myeloma: a review of targets, drugs, clinical trials and future directions. Front Immunol 2020; Apr 11: 501
- 28 Cho SF, Lin L, Xing L, Li Y, Yu T, Anderson KC. et al. BMCA-targeting therapy: driving a new era of immunotherapy of multiple mieloma. Cancers (Basel) 2020; Jun 12 (06) 1473
- 29 Shah N, Aiello J, Avigan DE, Berdeja JG, Borrello IM, Chari A. et al. The Society for Immunotherapy of cancer consensus statement on immunotherapy for the treatment of multiple myeloma. J Immunother Cancer 2020; Jul 8 (02) e000734
- 30 Radhakrishnan S, Luetkens T, Scherer SD, Davis P, Mause ERV, Olson ML. et al. CD229 CAR T-cell eliminate multiple myeloma and tumor propagating cells without fratricide. Nat Commun 2020; Feb 11 (01) 798