bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2025-70-2-252-263bloodjour-640Research ArticleОБЗОРЫREVIEWSНовые стратегии в лечении рефрактерных форм и рецидивов фолликулярной лимфомы: терапия Т-лимфоцитами с химерным антигенным рецепторомNew strategies in the treatment of refractory forms and relapses of follicular lymphoma: CAR T-cell therapyhttps://orcid.org/0000-0003-0591-2589СмольяниноваА. К.SmolyaninovaA. K.

Смольянинова Анна Константиновна - кандидат медицинских наук, научный сотрудник, гематолог отделения гематологии и химиотерапии лимфом с блоком трансплантации костного мозга и гемопоэтических стволовых клеток.

125167, Москва

Anna K. Smolianinova - Cand. Sci. (Med.), Hematologist, Department of Hematology and Chemotherapy of Lymphomas with Bone Marrow and Hematopoietic Stem Cell Transplantation Unit.

Moscow

annmo8@mail.ruhttps://orcid.org/0000-0002-9969-8482АлешинаО. А.AleshinaO. A.

Алешина Ольга Александровна - кандидат медицинских наук, заведующая отделом клеточной и иммунной терапии, гематолог отделения гематологии и химиотерапии острых лейкозов и лимфом.

125167, Москва

Olga A. Aleshina - Cand. Sci. (Med.), Head of cell and immunotherapy department.

Moscow

dr.gavrilina@mail.ruhttps://orcid.org/0000-0002-8664-6341БоголюбоваА. В.BogolyubovaA. V.

Боголюбова Аполлинария Васильевна - кандидат биологических наук, заведующая лабораторией трансплантационной иммунологии.

125167, Москва

Apolinaria V. Bogolyubova - Cand. Sci. (Biol.), Head of Laboratory of transplantation immunology.

Moscow

apollinariya.bogolyubova@gmail.comhttps://orcid.org/0000-0002-2639-7419ЗвонковЕ. Е.ZvonkovE. E.

Звонков Евгений Евгеньевич - доктор медицинских наук, заведующий отделением гематологии и химиотерапии лимфом с блоком трансплантации костного мозга и гемопоэтических стволовых клеток.

125167, Москва

Evgeny E. Zvonkov - Dr. Sci. (Med.), Head of the Department of Hematology and Chemotherapy of Lymphomas with Bone Marrow and Hematopoietic Stem Cell Transplantation Unit.

Moscow

zvonkov@blood.ruФГБУ «Национальный медицинский исследовательский центр гематологии» Министерства здравоохранения Российской ФедерацииРоссияNational Medical Research Center for HematologyRussian Federation202510072025702252263Copyright © Смольянинова А.К., Алешина О.А., Боголюбова А.В., Звонков Е.Е., 20252025Смольянинова А.К., Алешина О.А., Боголюбова А.В., Звонков Е.Е.Smolyaninova A.K., Aleshina O.A., Bogolyubova A.V., Zvonkov E.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/640Введение

Введение. Фолликулярная лимфома (ФЛ) — самая частая индолентная лимфома. Несмотря на продолжительную общую выживаемость, опухоль остается неизлечимой у большинства больных. Не существует алгоритма выбора лечения ФЛ после 3 линий терапии. Терапия Т-лимфоцитами с химерным антигенным рецептором (chimeric antigen receptor, СAR) оказалась эффективной при ФЛ.

Цель

Цель: систематизировать данные об эффективности и безопасности современной CAR T терапии при ФЛ.

Основные сведения

Основные сведения. CAR T терапия — это лечебная опция для больных ФЛ как после множества курсов терапии, так и с первично рефрактерной опухолью. Продолжается совершенствование этого метода, улучшается безопасность и расширяются возможности использования, проводится интеграция CAR T терапии в противорецидивные схемы ФЛ.

Introduction

Introduction. Follicular lymphoma (FL) is the most common indolent lymphoma. Despite the long overall survival, the tumor remains incurable in most patients. Currently, there is no specific algorithm for choosing therapy for ≥3 lines of patients with FL. CAR T-cell therapy (therapy with genetically modified T-lymphocytes carrying a chimeric antigen receptor — CAR) has proven effective in many tumors, including FL.

Aim

Aim. to systematize data on the efficacy and safety of modern CAR T-cell therapy for follicular lymphoma.

Main findings

Main findings. CAR T-cell therapy is an effective option both for patients with FL after multiple courses of therapy, and for refractory tumors. Ongoing advancements continue to refine this method, enhancing its safety and expanding the possibilities of use. CAR T-cell therapy is increasingly being integrated into anti-relapse regimens for FL.

фолликулярная лимфомаCAR T терапиярецидиврефрактерностьfollicular lymphomaCAR T cell therapyrelapserefractory tumorработа выполнена в соответствии с государственным заданием «Исследование эффективности и безопасности CAR T-лимфоцитов 2-го поколения, специфичных к CD19 антигену В-клеток, у взрослых пациентов с рецидивами и рефрактерными формами В-клеточных лимфопролиферативных заболеваний» РК № 124012300248–3the study was performed in accordance with the State Assignment ‘Study of efficacy and safety of CAR T lymphocytes of the 2nd generation, specifi c to CD19 antigen of B-cells, in adult patients with relapsed and refractory forms of B-cell lymphoproliferative diseases’ № 124012300248-3ReferencesMorton L.M., Wang S.S., Devesa S.S., et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood. 2006;107(1):265–76. DOI: 10.1182/blood-2005-06-2508.Morton L.M., Wang S.S., Devesa S.S., et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood. 2006;107(1):265–76. DOI: 10.1182/blood-2005-06-2508.Watanabe T., Tobinai K., Wakabayashi M., et al. R-CHOP treatment for patients with advanced follicular lymphoma: Over 15-year follow-up of JCOG0203. Br J Haematol. 2024;204(3):849–60. DOI: 10.1111/bjh.19213.Watanabe T., Tobinai K., Wakabayashi M., et al. R-CHOP treatment for patients with advanced follicular lymphoma: Over 15-year follow-up of JCOG0203. Br J Haematol. 2024;204(3):849–60. DOI: 10.1111/bjh.19213.Ghione P., Palomba M.L., Ghesquieres H., et al. Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study. Haematologica. 2023;108(3):822–32. DOI: 10.3324/ HAEMATOL.2022.281421.Ghione P., Palomba M.L., Ghesquieres H., et al. Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study. Haematologica. 2023;108(3):822–32. DOI: 10.3324/HAEMATOL.2022.281421.Casulo C., Dixon J.G., Le-Rademacher J., et al. Validation of POD24 as a robust early clinical end point of poor survival in FL from 5225 patients on 13 clinical trials. Blood. 2022;139(11):1684–93. DOI: 10.1182/blood.2020010263.Casulo C., Dixon J.G., Le-Rademacher J., et al. Validation of POD24 as a robust early clinical end point of poor survival in FL from 5225 patients on 13 clinical trials. Blood. 2022;139(11):1684–93. DOI: 10.1182/blood.2020010263.Metzner B., Pott C., Müller T.H., et al. Long‐term outcome in patients with follicular lymphoma following high‐dose therapy and autologous stem cell transplantation. Eur J Haematol. 2021;107(5):543–52. DOI: 10.1111/ejh.13691.Metzner B., Pott C., Müller T.H., et al. Long‐term outcome in patients with follicular lymphoma following high‐dose therapy and autologous stem cell transplantation. Eur J Haematol. 2021;107(5):543–52. DOI: 10.1111/ejh.13691.Jiménez-Ubieto A., Grande C., Caballero D., et al. Autologous Stem Cell Transplantation for Follicular Lymphoma: Favorable Long-Term Survival Irrespective of Pretransplantation Rituximab Exposure. Biol Blood Marrow Transplant. 2017;23(10):1631–40. DOI: 10.1016/j.bbmt.2017.05.021.Jiménez-Ubieto A., Grande C., Caballero D., et al. Autologous Stem Cell Transplantation for Follicular Lymphoma: Favorable Long-Term Survival Irrespective of Pretransplantation Rituximab Exposure. Biol Blood Marrow Transplant. 2017;23(10):1631–40. DOI: 10.1016/j.bbmt.2017.05.021.Смольянинова А.К., Беляева А.В., Сидорова Ю.В. и др. Высокодозная химиотерапия с трансплантацией аутологичных гемопоэтических стволовых клеток в первой линии терапии фолликулярной лимфомы. Гематология и трансфузиология. 2023;68(3):344–62. DOI: 10.35754/0234-5730-2023-68-3-344-362.Smolyaninova A.K., Belyayeva A. V., Sidorova Y. V., et al. High-dose chemotherapy with transplantation of autologous hematopoietic stem cells in the fi rst line of follicular lymphoma therapy. Gematologiya I Transfusiologiya. 2023;68(3):344– 62 (In Russian). DOI: 10.35754/0234-5730-2023-68-3-344-362.Giraudo M., Jackson Z., Das I., et al. Chimeric Antigen Receptor (CAR)-T Cell Therapy for Non-Hodgkin’s Lymphoma. Pathogens and Immunity. 2024;9(1):1–17. DOI: 10.20411/pai.v9i1.647.Giraudo M., Jackson Z., Das I., et al. Chimeric Antigen Receptor (CAR)-T Cell Therapy for Non-Hodgkin’s Lymphoma. Pathogens and Immunity. 2024;9(1):1–17. DOI: 10.20411/pai.v9i1.647.Гаврилина О.А., Галстян Г.М., Щекина А.Е. и др. Терапия Т-клетками с химерным антигенным рецептором взрослых больных В-клеточными лимфопролиферативными заболеваниям. Гематология и трансфузиология. 2022;67(1):8–28. DOI: 10.35754/0234-5730-2022-67-1-8-28.Gavrilina O.A., Galstyan G.M., Shchekina A.E., et al. Chimeric antigen receptor T-cell therapy in adult patients with B-cell lymphoproliferative diseases. Gematologiya I Transfusiologiya. 2022;67(1):8–28 (In Russian). DOI: 10.35754/02345730-2022-67-1-8-28.Jacobs R., Jacobson C. The treatment of follicular lymphoma with CD19-directed chimeric antigen receptor T-cell therapy. Front Oncol. 2024;14:1384600. DOI: 10.3389/fonc.2024.1384600.Jacobs R., Jacobson C. The treatment of follicular lymphoma with CD19-directed chimeric antigen receptor T-cell therapy. Front Oncol. 2024;14: 1384600. DOI: 10.3389/fonc.2024.1384600.Fowler N.H., Chavez J.C., Riedell P.A. Moving T-Cell Therapies into the Standard of Care for Patients with Relapsed or Refractory Follicular Lymphoma: A Review. Target Oncol. 2024;19(4):495–510. DOI: 10.1007/s11523-024-01070-z.Fowler N.H., Chavez J.C., Riedell P.A. Moving T-Cell Therapies into the Standard of Care for Patients with Relapsed or Refractory Follicular Lymphoma: A Review. Target Oncol. 2024;19(4):495–510. DOI: 10.1007/s11523-024-01070-z.Thiruvengadam S.K., Shouse G., Danilov A. V. Thinking “outside the germinal center”: Re-educating T cells to combat follicular lymphoma. Blood Rev. 2023;61:101099. DOI: 10.1016/j.blre.2023.101099.Thiruvengadam S.K., Shouse G., Danilov A. V. Thinking “outside the germinal center”: Re-educating T cells to combat follicular lymphoma. Blood Rev. 2023;61:101099. DOI: 10.1016/j.blre.2023.101099.Perica K., Curran K.J., Brentjens R.J., et al. Building a CAR Garage: Preparing for the Delivery of Commercial CAR T Cell Products at Memorial Sloan Kettering Cancer Center. Biol Blood Marrow Transplant. 2018;24(6):1135–41. DOI: 10.1016/j.bbmt.2018.02.018.Perica K., Curran K.J., Brentjens R.J., et al. Building a CAR Garage: Preparing for the Delivery of Commercial CAR T Cell Products at Memorial Sloan Kettering Cancer Center. Biol Blood Marrow Transplant. 2018;24(6):1135–41. DOI: 10.1016/j.bbmt.2018.02.018.Ayala Ceja M., Khericha M., Harris C.M., et al. CAR-T cell manufacturing: Major process parameters and next-generation strategies. J Exp Med. 2024;221(2):e20230903. DOI: 10.1084/jem.20230903.Ayala Ceja M., Khericha M., Harris C.M., et al. CAR-T cell manufacturing: Major process parameters and next-generation strategies. J Exp Med. 2024;221(2):e20230903. DOI: 10.1084/jem.20230903.Lickefett B., Chu L., Ortiz-Maldonado V., et al. Lymphodepletion — an essential but undervalued part of the chimeric antigen receptor T-cell therapy cycle. Front Immunol. 2023;14: 1303935. DOI: 10.3389/fimmu.2023.1303935.Lickefett B., Chu L., Ortiz-Maldonado V., et al. Lymphodepletion — an essential but undervalued part of the chimeric antigen receptor T-cell therapy cycle. Front Immunol. 2023;14:1303935. DOI: 10.3389/fimmu.2023.1303935.Chong E.A., Chong E.R., Therwhanger D., et al. Bendamustine as Lymphodepletion for Brexucabtagene Autoleucel Therapy of Mantle Cell Lymphoma. Transplant Cell Ther. 2024;30(7):726.e1–e8. DOI: 10.1016/j.jtct.2024.03.015.Chong E.A., Chong E.R., Therwhanger D., et al. Bendamustine as Lymphodepletion for Brexucabtagene Autoleucel Therapy of Mantle Cell Lymphoma. Transplant Cell Ther. 2024;30(7):726.e1–e8. DOI: 10.1016/j.jtct.2024.03.015.Ghilardi G., Chong E.A., Svoboda J., et al. Bendamustine is safe and effective for lymphodepletion before tisagenlecleucel in patients with refractory or relapsed large B-cell lymphomas. Ann Oncol. 2022;33(9):916–28. DOI: 10.1016/j.annonc.2022.05.521.Ghilardi G., Chong E.A., Svoboda J., et al. Bendamustine is safe and effective for lymphodepletion before tisagenlecleucel in patients with refractory or relapsed large B-cell lymphomas. Ann Oncol. 2022;33(9):916–28. DOI: 10.1016/j.annonc.2022.05.521.Eshhar Z., Waks T., Gross G., et al. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Nat Acad Sci. 1993;90(2):720–4. DOI: 10.1073/pnas.90.2.720.Eshhar Z., Waks T., Gross G., et al. Specifi c activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Nat Acad Sci. 1993;90(2):720–4. DOI: 10.1073/pnas.90.2.720.Till B.G., Jensen M.C., Wang J., et al. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood. 2008;112(6):2261–71. DOI: 10.1182/blood-2007-12-128843.Till B.G., Jensen M.C., Wang J., et al. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modifi ed autologous CD20-specifi c T cells. Blood. 2008;112(6):2261–71. DOI: 10.1182/blood-2007-12-128843.Kershaw M.H., Westwood J.A., Parker L.L., et al. A Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer. Clin Cancer Res. 2006;12(20):6106–15. DOI: 10.1158/1078-0432.CCR-06-1183.Kershaw M.H., Westwood J.A., Parker L.L., et al. A Phase I Study on Adoptive Immunotherapy Using Gene-Modifi ed T Cells for Ovarian Cancer. Clin Cancer Res. 2006;12(20):6106–15. DOI: 10.1158/1078-0432.CCR-06-1183.van der Stegen S.J.C., Hamieh M., Sadelain M. The pharmacology of second-generation chimeric antigen receptors. Nat Rev Drug Disccov. 2015;14(7):499– 509. DOI: 10.1038/nrd4597.van der Stegen S.J.C., Hamieh M., Sadelain M. The pharmacology of secondgeneration chimeric antigen receptors. Nat Rev Drug Disccov. 2015;14(7):499– 509. DOI: 10.1038/nrd4597.Savoldo B., Ramos C.A., Liu E., et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor–modified T cells in lymphoma patients. J Clin Invest. 2011;121(5):1822–6. DOI: 10.1172/JCI46110.Savoldo B., Ramos C.A., Liu E., et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor–modifi ed T cells in lymphoma patients. J Clin Invest. 2011;121(5):1822–6. DOI: 10.1172/JCI46110.Abramson J.S., Palomba M.L., Gordon L.I., 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– 52. DOI: 10.1016/S0140-6736(20)31366-0.Abramson J.S., Palomba M.L., Gordon L.I., 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– 52. DOI: 10.1016/S0140-6736(20)31366-0.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):1331–42. DOI: 10.1056/NEJMOA1914347.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):1331–42. DOI: 10.1056/NEJMOA1914347.Locke F.L., Ghobadi A., Jacobson C.A., 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.Locke F.L., Ghobadi A., Jacobson C.A., 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.Schuster S.J., Bishop M.R., Tam C.S., 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.Schuster S.J., Bishop M.R., Tam C.S., 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.Kochenderfer J.N., Wilson W.H., Janik J.E., et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. 2010;116(20):4099–102. DOI: 10.1182/BLOOD-2010-04-281931.Kochenderfer J.N., Wilson W.H., Janik J.E., et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. 2010;116(20):4099–102. DOI: 10.1182/BLOOD-2010-04-281931.Cappell K.M., Sherry R.M., Yang J.C., et al. Long-Term Follow-Up of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy. J Clin Oncol. 2020;38(32):3805–15. DOI: 10.1200/JCO.20.01467.Cappell K.M., Sherry R.M., Yang J.C., et al. Long-Term Follow-Up of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy. J Clin Oncol. 2020;38(32):3805–15. DOI: 10.1200/JCO.20.01467.Schuster S.J., Svoboda J., Chong E.A., et al. Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. 2017;377(26):2545–54. DOI: 10.1056/NEJMoa1708566.Schuster S.J., Svoboda J., Chong E.A., et al. Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. 2017;377(26):2545–54. DOI: 10.1056/NEJMoa1708566.Kochenderfer J.N., Dudley M.E., Kassim S.H., et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol. 2015;33(6):540–9. DOI: 10.1200/JCO.2014.56.2025.Kochenderfer J.N., Dudley M.E., Kassim S.H., et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol. 2015;33(6):540–9. DOI: 10.1200/JCO.2014.56.2025.Jacobson C.A., Chavez J.C., Sehgal A.R., 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. DOI: 10.1016/s1470-2045(21)00591-X.Jacobson C.A., Chavez J.C., Sehgal A.R., 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. DOI: 10.1016/s1470-2045(21)00591-X.Schuster S.J., Fowler N., Dickinson M., et al. Clinical Outcomes of Patients with Relapsed/Refractory Follicular Lymphoma Treated with Tisagenlecleucel: Phase 2 Elara 3-Year Follow-up. Blood. 2023;142(Suppl. 1):601. DOI: 10.1182/ blood-2023-180936.Schuster S.J., Fowler N., Dickinson M., et al. Clinical Outcomes of Patients with Relapsed/Refractory Follicular Lymphoma Treated with Tisagenlecleucel: Phase 2 Elara 3-Year Follow-up. Blood. 2023;142(Suppl. 1):601. DOI: 10.1182/blood-2023-180936.Solal-Celigny P. Follicular Lymphoma International Prognostic Index. Blood. 2004;104(5):1258–65. DOI: 10.1182/blood-2003-12-4434.Solal-Celigny P. Follicular Lymphoma International Prognostic Index. Blood. 2004;104(5):1258–65. DOI: 10.1182/blood-2003-12-4434.Neelapu S.S., Chavez J.C., Sehgal A.R., et al. Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: 4-Year Follow-up from the Phase 2 ZUMA-5 Trial. Blood. 2023;142(Supplement 1):4868. DOI: 10.1182/blood-2023-174914.Neelapu S.S., Chavez J.C., Sehgal A.R., et al. Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: 4-Year Follow-up from the Phase 2 ZUMA-5 Trial. Blood. 2023;142(Supplement 1):4868. DOI: 10.1182/blood-2023-174914.Zelenetz A.D., Gordon L.I., Abramson J.S., et al. NCCN Guidelines Insights: BCell Lymphomas, Version 3.2019. J Natl Compr Cancer Netw. 2019;17(6):650– 61. DOI: 10.6004/jnccn.2019.0029.Zelenetz A.D., Gordon L.I., Abramson J.S., et al. NCCN Guidelines Insights: BCell Lymphomas, Version 3.2019. J Natl Compr Cancer Netw. 2019;17(6):650– 61. DOI: 10.6004/jnccn.2019.0029.Fowler N.H., 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.Fowler N.H., 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.Mor V., Laliberte L., Morris J.N., et al. The Karnofsky performance status scale: An examination of its reliability and validity in a research setting. Cancer. 1984;53(9):2002–7. DOI: 10.1002/1097-0142(19840501)53:9<2002::AIDCNCR2820530933>3.0.CO;2-W.Mor V., Laliberte L., Morris J.N., et al. The Karnofsky performance status scale: An examination of its reliability and validity in a research setting. Cancer. 1984;53(9):2002–7. DOI: 10.1002/1097-0142(19840501)53:9<2002::AIDCNCR2820530933>3.0.CO;2-W.Azoulay É., Castro P., Maamar A., et al. Outcomes in patients treated with chimeric antigen receptor T-cell therapy who were admitted to intensive care (CARTTAS): an international, multicentre, observational cohort study. Lancet Haematol. 2021;8(5):e355–64. DOI: 10.1016/S2352-3026(21)00060-0.Azoulay É., Castro P., Maamar A., et al. Outcomes in patients treated with chimeric antigen receptor T-cell therapy who were admitted to intensive care (CARTTAS): an international, multicentre, observational cohort study. Lancet Haematol. 2021;8(5):e355–64. DOI: 10.1016/S2352-3026(21)00060-0.Щекина А.Е., Галстян Г.М., Гаврилина О.А., и др.. Синдром высвобождения цитокинов и другие осложнения после терапии Т-лимфоцитами с химерным антигенным рецептором у взрослых с В-клеточными лимфомами и лейкозами. Гематология и трансфузиология. 2022;67(S2.):88.Щекина А.Е., Галстян Г.М., Гаврилина О.А., и др.. Синдром высвобождения цитокинов и другие осложнения после терапии Т-лимфоцитами с химерным антигенным рецептором у взрослых с В-клеточными лимфомами и лейкозами. Гематология и трансфузиология. 2022;67(S2.):88.Neelapu S.S., Tummala S., Kebriaei P., et al. Chimeric antigen receptor Tcell therapy — assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15(1):47–62. DOI: 10.1038/nrclinonc.2017.148.Neelapu S.S., Tummala S., Kebriaei P., et al. Chimeric antigen receptor Tcell therapy — assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15(1):47–62. DOI: 10.1038/nrclinonc.2017.148.Kymriah® (tisagenlecleucel) [package insert]. East Hanover (NJ): Novartis Pharmaceuticals Corporation; 2022.Kymriah® (tisagenlecleucel) [package insert]. East Hanover (NJ): Novartis Pharmaceuticals Corporation; 2022.Yescarta® (axicabtagene ciloleucel) [package insert]. Santa Monica (CA): Kite Pharma, Inc.; 2022.Yescarta® (axicabtagene ciloleucel) [package insert]. Santa Monica (CA): Kite Pharma, Inc.; 2022.Adkins, S. CAR T-Cell Therapy: Adverse Events and Management. J Adv Pract Oncol. 2019;10(Suppl 3): 21–28. DOI: 10.6004/jadpro.2019.10.4.11.Adkins, S. CAR T-Cell Therapy: Adverse Events and Management. J Adv Pract Oncol. 2019;10(Suppl 3): 21–28. DOI: 10.6004/jadpro.2019.10.4.11.Jacobson C.A., Hemmer M.T., Hu Z.-H., et al. Real-world early outcomes of axicabtagene ciloleucel for relapsed or refractory (R/R) follicular lymphoma (FL). J Clin Oncol. 2023;41(16_suppl):7509. DOI: 10.1200/JCO.2023.41.16_suppl.7509.Jacobson C.A., Hemmer M.T., Hu Z.-H., et al. Real-world early outcomes of axicabtagene ciloleucel for relapsed or refractory (R/R) follicular lymphoma (FL). J Clin Oncol. 2023;41(16_suppl):7509. DOI: 10.1200/JCO.2023.41.16_suppl.7509.Ghafouri S., Fenerty K., Schiller G., et al. Real-World Experience of Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed or Refractory Aggressive B-cell Lymphomas: A Single-Institution Experience. Clin Lymphoma Myeloma Leuk. 2021;21(12):861–72. DOI: 10.1016/j.clml.2021.07.002.Ghafouri S., Fenerty K., Schiller G., et al. Real-World Experience of Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed or Refractory Aggressive B-cell Lymphomas: A Single-Institution Experience. Clin Lymphoma Myeloma Leuk. 2021;21(12):861–72. DOI: 10.1016/j.clml.2021.07.002.Kwon M., Iacoboni G., Reguera J.L., et al. Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma. Haematologica. 2022;108(1):110–21. DOI: 10.3324/haematol.2022.280805.Kwon M., Iacoboni G., Reguera J.L., et al. Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma. Haematologica. 2022;108(1):110–21. DOI: 10.3324/haematol.2022.280805.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 Lymph. 2024;65(3):323–32. DOI: 10.1080/10428194.2023.2289854.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 Lymph. 2024;65(3):323–32. DOI: 10.1080/10428194.2023.2289854.Flinn I.W., Jacobson C.A., Nastoupil L.J., et al. ZUMA-22: A phase 3, randomized controlled study of axicabtagene ciloleucel (axi-cel) versus standard-ofcare therapy in patients with relapsed or refractory (R/R) follicular lymphoma (FL). J Clin Oncol. 2023;41(16_suppl):TPS7579. DOI: 10.1200/JCO.2023.41.16_suppl.TPS7579.Flinn I.W., Jacobson C.A., Nastoupil L.J., et al. ZUMA-22: A phase 3, randomized controlled study of axicabtagene ciloleucel (axi-cel) versus standard-ofcare therapy in patients with relapsed or refractory (R/R) follicular lymphoma (FL). J Clin Oncol. 2023;41(16_suppl):TPS7579. DOI: 10.1200/JCO.2023.41.16_suppl.TPS7579.Ghione P., Palomba M.L., Patel A.R., et al. Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma. Blood. 2022;140(8):851–60. DOI: 10.1182/blood.2021014375.Ghione P., Palomba M.L., Patel A.R., et al. Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma. Blood. 2022;140(8):851–60. DOI: 10.1182/blood.2021014375.Salles G., Schuster S.J., Dreyling M., et al. Efficacy comparison of tisagenlecleucel vs usual care in patients with relapsed or refractory follicular lymphoma. Blood Adv. 2022;6(22):5835–43. DOI: 10.1182/bloodadvances.2022008150.Salles G., Schuster S.J., Dreyling M., et al. Efficacy comparison of tisagenlecleucel vs usual care in patients with relapsed or refractory follicular lymphoma. Blood Adv. 2022;6(22):5835–43. DOI: 10.1182/bloodadvances.2022008150.Visco C., Chiappella A., Nassi L., et al. Rituximab, bendamustine, and lowdose cytarabine as induction therapy in elderly patients with mantle cell lymphoma: a multicentre, phase 2 trial from Fondazione Italiana Linfomi. Lancet Haematol. 2017;4(1):e15–23. DOI: 10.1016/S2352-3026(16)30185-5.Visco C., Chiappella A., Nassi L., et al. Rituximab, bendamustine, and lowdose cytarabine as induction therapy in elderly patients with mantle cell lymphoma: a multicentre, phase 2 trial from Fondazione Italiana Linfomi. Lancet Haematol. 2017;4(1):e15–23. DOI: 10.1016/S2352-3026(16)30185-5.Neelapu S.S., Chavez J., Sehgal A.R., et al. 3-Year Follow-up Analysis of ZUMA-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL). Blood. 2022;140(Supplement 1):10380–3. DOI: 10.1182/blood-2022-156120.Neelapu S.S., Chavez J., Sehgal A.R., et al. 3-Year Follow-up Analysis of ZUMA-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL). Blood. 2022;140(Supplement 1):10380–3. DOI: 10.1182/blood-2022-156120.Iacoboni G., Navarro V., Martín-López A.Á., et al. Recent Bendamustine Treatment Before Apheresis Has a Negative Impact on Outcomes in Patients With 1984;53(9):2002–7. DOI: 10.1002/1097-0142(19840501)53:9<2002::AIDCNCR2820530933>3.0.CO;2-W.Iacoboni G., Navarro V., Martín-López A.Á., et al. Recent Bendamustine Treatment Before Apheresis Has a Negative Impact on Outcomes in Patients With Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy. J Clin Oncol. 2024;42(2):205–17. DOI: 10.1200/JCO.23.01097.Yakoub-Agha I., Chabannon C., Bader P., et al. Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Haematologica. 2020;105(2):297–316. DOI: 10.3324/haematol.2019.229781.Yakoub-Agha I., Chabannon C., Bader P., et al. Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Haematologica. 2020;105(2):297–316. DOI: 10.3324/haematol.2019.229781.Casulo C., Friedberg J.W., Ahn K.W., et al. Autologous Transplantation in Follicular Lymphoma with Early Therapy Failure: A National LymphoCare Study and Center for International Blood and Marrow Transplant Research Analysis. Biol Blood Marrow Transplant. 2018;24(6):1163–71. DOI: 10.1016/j.bbmt.2017.12.771.Casulo C., Friedberg J.W., Ahn K.W., et al. Autologous Transplantation in Follicular Lymphoma with Early Therapy Failure: A National LymphoCare Study and Center for International Blood and Marrow Transplant Research Analysis. Biol Blood Marrow Transplant. 2018;24(6):1163–71. DOI: 10.1016/j.bbmt.2017.12.771.Locke F.L., Miklos D.B., Jacobson C.A., et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022;386(7):640– 54. DOI: 10.1056/NEJMoa2116133.Locke F.L., Miklos D.B., Jacobson C.A., et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022;386(7):640– 54. DOI: 10.1056/NEJMoa2116133.Shadman M., Caimi P.F., O’Brien S.M., et al. Efficacy and Safety of a Third Generation CD20 CAR-T (MB-106) for Treatment of Relapsed/Refractory Indolent B-Cell Non-Hodgkin Lymphoma: Phase-1 Results from a Multicenter Trial. Blood. 2023;142(Suppl. 1):2102. DOI: 10.1182/blood-2023-175007.Shadman M., Caimi P.F., O’Brien S.M., et al. Efficacy and Safety of a Third Generation CD20 CAR-T (MB-106) for Treatment of Relapsed/Refractory Indolent B-Cell Non-Hodgkin Lymphoma: Phase-1 Results from a Multicenter Trial. Blood. 2023;142(Suppl. 1):2102. DOI: 10.1182/blood-2023-175007.Shah N.N., Johnson B.D., Schneider D., et al. Bispecific anti-CD20, antiCD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial. Nature Med. 2020;26(10):1569–75. DOI: 10.1038/s41591-020-1081-3.Shah N.N., Johnson B.D., Schneider D., et al. Bispecifi c anti-CD20, antiCD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial. Nature Med. 2020;26(10):1569–75. DOI: 10.1038/s41591-020-1081-3.Tong C., Zhang Y., Liu Y., et al. Optimized tandem CD19/CD20 CAR-engineered T cells in refractory/relapsed B cell lymphoma. Blood. 2020; 135 (14): 1632–44. DOI: 10.1182/blood.2020005278.Tong C., Zhang Y., Liu Y., et al. Optimized tandem CD19/CD20 CARengineered T cells in refractory/relapsed B cell lymphoma. Blood. 2020; 135 (14):1632–44. DOI: 10.1182/blood.2020005278.Locke F.L., Munoz J.L., Tees M.T., et al. ALLO-647 for Lymphodepletion in the Allogeneic CAR T Setting: Safety Experience with ALLO-501/501A in Patients (Pts) with Relapsed/Refractory (r/r) Large B-Cell and Follicular Lymphomas. Blood. 2023;142 (Suppl. 1):2095. DOI: 10.1182/blood-2023-189196.Locke F.L., Munoz J.L., Tees M.T., et al. ALLO-647 for Lymphodepletion in the Allogeneic CAR T Setting: Safety Experience with ALLO-501/501A in Patients (Pts) with Relapsed/Refractory (r/r) Large B-Cell and Follicular Lymphomas. Blood. 2023;142 (Suppl. 1):2095. DOI: 10.1182/blood-2023-189196

The authors declare that there are no conflicts of interest present.