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Role of bridging RT in relapsed/refractory diffuse large B-cell lymphoma undergoing CAR-T therapy: a multicenter study

Bone Marrow Transplantation volume 60, pages 32–38 (2025)Cite this article

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Abstract

The optimization of bridging regimen before chimeric antigen receptor (CAR)-T cell therapy in diffuse large B-cell lymphoma (DLBCL) may impact CAR-T efficacy and outcome. This retrospective study evaluates CAR-T outcome after bridging with radiotherapy (RT) and other bridging strategies. Among 148 patients with relapsed/refractory DLBCL who underwent leukapheresis for CAR-T manufacturing, 31 received RT-bridging, 84 chemotherapy (CT), 33 no-bridging or steroid-only. CAR-T cell were infused in 96.8% of RT-group, 89.2% of CT-group and 78.8% of no-bridge-group (p = 0.079). Response to bridging was generally poor, but patients receiving RT had a significant reduction in LDH levels between pre- and post-bridging (p = 0.05). The one-year PFS was 51.2% in the RT-group, 28.2% in the CT-group, and 47.6% in the no-bridge-group (p = 0.044, CT-bridging vs RT-bridging); 1-year OS was 86.7% in the RT-group, 52.7% in the CT-group and 69% in the no-bridge-group (p = 0.025, CT-bridging vs RT-bridging). We observed a higher incidence of ICANS in patients who received CT than in others (20.0% CT-group, 3.3% RT-group, 7.7% no-bridge group; p = 0.05). In conclusion, RT-bridging is associated with lower drop-out rate and CAR-T toxicity, and it might be preferred to other bridging strategies for patients with localized disease or for those with one prevalent symptomatic site.

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Data availability

Informed consent was obtained from all participants. The datasets generated during and analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Westin JR, Kersten MJ, Salles G, Abramson JS, Schuster SJ, Locke FL, et al. Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. Am J Hematol. 2021;96:1295–312.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ababneh HS, Abramson JS, Johnson PC, Patel CG. Assessing the role of radiotherapy in patients with refractory or relapsed high-grade B-cell lymphomas treated with CAR T-cell therapy. Radiother Oncol. 2022;175:65–72.

    Article  PubMed  Google Scholar 

  3. Nastoupil LJ, Jain MD, Feng L, Spiegel JY, Ghobadi A, Lin Y, et al. Standard-of-care axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma: results from the US lymphoma CAR T consortium. J Clin Oncol. 2020;38:3119–28.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Amini L, Silbert SK, Maude SL, Nastoupil LJ, Ramos CA, Brentjens RJ, et al. Preparing for CAR T cell therapy: patient selection, bridging therapies and lymphodepletion. Nat Rev Clin Oncol. 2022;19:342–55.

    Article  PubMed  Google Scholar 

  5. Sim AJ, Jain MD, Figura NB, Shah BD, Khimani F, Lazaryan A, et al. Radiation Therapy as a Bridging Strategy for CAR T Cell Therapy With Axicabtagene Ciloleucel in Diffuse Large B-Cell Lymphoma. Int J Radiat Oncol Biol Phys. 2019;105:1012–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, 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;20:31–42.

    Article  CAS  PubMed  Google Scholar 

  7. Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N. Engl J Med. 2019;380:45–56.

    Article  CAS  PubMed  Google Scholar 

  8. Bethge WA, Martus P, Schmitt M, Holtick U, Subklewe M, von Tresckow B, et al. GLA/DRST real-world outcome analysis of CAR T-cell therapies for large B-cell lymphoma in Germany. Blood. 2022;140:349–58.

    CAS  PubMed  Google Scholar 

  9. Frey N. Cytokine release syndrome: Who is at risk and how to treat. Best Pr Res Clin Haematol. 2017;30:336–40.

    Article  Google Scholar 

  10. Martens C, Hodgson DC, Wells WA, Sun A, Bezjak A, Pintilie M, et al. Outcome of hyperfractionated radiotherapy in chemotherapy-resistant non-Hodgkin’s lymphoma. Int J Radiat Oncol Biol Phys. 2006;64:1183–7.

    Article  PubMed  Google Scholar 

  11. Tseng YD, Chen YH, Catalano PJ, Ng A. Rates and durability of response to salvage radiation therapy among patients with refractory or relapsed aggressive non-Hodgkin lymphoma. Int J Radiat Oncol Biol Phys. 2015;91:223–31.

    Article  PubMed  Google Scholar 

  12. Kim A, Stevenson P, Cassaday RD, Soma L, Fromm JR, Gopal AK, et al. Impact of double- or triple-hit pathology on rates and durability of radiation therapy response among patients with relapsed or refractory large B-cell lymphoma. Pr Radiat Oncol. 2020;10:44–52.

    Article  Google Scholar 

  13. Dewey WC, Ling CC, Meyn RE. Radiation-induced apoptosis: relevance to radiotherapy. Int J Radiat Oncol Biol Phys. 1995;33:781–96.

    Article  CAS  PubMed  Google Scholar 

  14. Liu Y, Dong Y, Kong L, Shi F, Zhu H, Yu J. Abscopal effect of radiotherapy combined with immune checkpoint inhibitors. J Hematol Oncol. 2018;11:104.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059–68.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transpl. 2019;25:625–38.

    Article  CAS  Google Scholar 

  17. Bachy E, Le Gouill S, Di Blasi R, Sesques P, Manson G, Cartron G, 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;28:2145–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Jain MD, Jacobs MT, Gao F, Nastoupil LJ, Spiegel JY, Lin Y, et al. Bridging therapy with axicabtagene ciloleucel for large B-cell lymphoma: Results from the US lymphoma CAR-T consortium. Blood Adv. 2023:bloodadvances.2023011489.

  19. Pinnix CC, Gunther JR, Dabaja BS, Strati P, Fang P, Hawkins MC, et al. Bridging therapy prior to axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma. Blood Adv. 2020;4:2871–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N. Engl J Med. 2017;377:2531–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gust J, Hay KA, Hanafi LA, Li D, Myerson D, Gonzalez-Cuyar LF, et al. Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T Cells. Cancer Discov. 2017;7:1404–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schultz L, Zurich MG, Culot M, da Costa A, Landry C, Bellwon P, et al. Evaluation of drug-induced neurotoxicity based on metabolomics, proteomics and electrical activity measurements in complementary CNS in vitro models. Toxicol Vitr. 2015;30:138–65.

    Article  CAS  Google Scholar 

  23. Soussain C, Ricard D, Fike JR, Mazeron JJ, Psimaras D, Delattre JY. CNS complications of radiotherapy and chemotherapy. Lancet. 2009;374:1639–51.

    Article  CAS  PubMed  Google Scholar 

  24. Vercellino L, Di Blasi R, Kanoun S, Tessoulin B, Rossi C, D’Aveni-Piney M, et al. Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2020;4:5607–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bachanova V, Westin J, Tam C, Borchmann P, Jaeger U, McGuirk J, et al. Correlative analyses of cytokine release syndrome and neurological events in tisagenlecleucel‐treated relapsed/refractory diffuse large B‐cell lymphoma patients. Hematol Oncol. 2019;37:308–10.

    Article  Google Scholar 

  26. Hubbeling H, Silverman EA, Michaud L, Tomas AA, Shouval R, Flynn J, et al. Bridging radiation rapidly and effectively cytoreduces high-risk relapsed/refractory aggressive B cell lymphomas prior to chimeric antigen receptor T cell therapy. Transpl Cell Ther. 2023;29:259.e1–259.e10.

    Article  CAS  Google Scholar 

  27. Ghafouri S, Fenerty K, Schiller G, de Vos S, Eradat H, Timmerman J, 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;21:861–72.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Editorial assistance was provided by Luca Giacomelli, PhD, Valentina Attanasio and Massimiliano Pianta; this assistance was supported by internal funds.

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Author notes

  1. These authors contributed equally: Stefania Bramanti, Daniele Mannina.

  2. These authors jointly supervised this work: Armando Santoro, Paolo Corradini.

Authors and Affiliations

  1. IRCCS Humanitas Research Hospital, Humanitas, Cancer Center, Milano, Rozzano Milano, Italy

    Stefania Bramanti, Daniele Mannina, Chiara De Philippis, Laura Giordano, Pierina Navarria, Pietro Mancosu, Daniela Taurino, Marta Scorsetti, Carmelo Carlo-Stella & Armando Santoro

  2. IRCCS Istituto Nazionale Tumori, Milano, Italy

    Annalisa Chiappella & Paolo Corradini

  3. IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy

    Beatrice Casadei & Pierluigi Zinzani

  4. Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy

    Pierluigi Zinzani

  5. Dept. of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy

    Armando Santoro

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  1. Stefania Bramanti
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  14. Paolo Corradini
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Contributions

SB, DM and AS designed the study. LG analysed the data. DM wrote the manuscript, with the revision and active contribution by SB, AS, PLZ and PC. CDP, DT, AC, BC, PN, MS, PM actively managed the patients and contributed in collecting the data.

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Correspondence to Daniele Mannina.

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Bramanti, S., Mannina, D., Chiappella, A. et al. Role of bridging RT in relapsed/refractory diffuse large B-cell lymphoma undergoing CAR-T therapy: a multicenter study. Bone Marrow Transplant 60, 32–38 (2025). https://doi.org/10.1038/s41409-024-02427-8

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