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Choice of commercially available CAR-T cell products for r/r DLBCL & PMBCL in Europe: a survey on behalf of the cellular therapy & immunobiology working party (CTIWP) of the EBMT

Bone Marrow Transplantation (2024)Cite this article

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Since summer 2018, three CAR-T cell products have been approved by the EMA to treat aggressive B-cell lymphomas, DLBCL, either de novo or tFL and PMBCL: tisagenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) [1,2,3]. Tisa-cel, axi-cel, and liso-cel are approved for the treatment of adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) (and primary mediastinal large B-cell lymphoma (PMBCL) for axi-cel and liso-cel). More recently, axi-cel and liso-cel were additionally approved for the treatment of adult patients with DLBCL and high-grade B-cell lymphoma (HGBL) (and PMBCL for liso-cel) that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy [2, 4, 5]. While the exact labelings of these products are different, there is a considerable overlap in product attributes and indications. There is so far no formal recommendations by medical experts or societies regarding the choice of one CAR-T cell product over another and no randomized trial addressed nor is likely to address the issue of the choice of the CAR-T cell products.

Therefore, to evaluate the real-world practices of the usage of CAR-T cells in aggressive lymphomas and capture the criteria used by centers to guide their choice of a product for a given patient, we conducted a survey on behalf of the Cellular Therapy and Immunobiology Working Party (CTIWP) of the EBMT. In June 2023 a questionnaire was sent to the 188 EBMT affiliated centers that have reported at least one CAR-T treatment in the registry, to collect the information regarding CAR-T cell products selected for the treatment of aggressive lymphoma, including DLBCL and PMBCL, but excluding mantle cell lymphoma, the process at the sites, clinical applications, and considerations guiding the choice of CAR-T cells at time of the survey. Over a 8-week period, three follow-up reminders regarding survey completion were sent, and the survey was closed in October 2023. Descriptive statistics were utilized to analyze the answers submitted by participating centers and the distribution of responses according to the questionnaire.

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Author notes

  1. These authors contributed equally: Annalisa Ruggeri, Florent Malard.

Authors and Affiliations

  1. Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Urban Novak & Michael Daskalakis

  2. EBMT Statistical Unit, Leiden, The Netherlands

    Jarl E. Mooyaart

  3. University of Cologne, Cologne, Germany

    Christof Scheid

  4. Hematology Department, CHU Montpellier, UMR5535, Université de Montpellier, Montpellier, France

    Ludovic Gabellier

  5. CHU de Lille, Lille, France

    Ibrahim Yakoub-Agha

  6. Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Ron Ram

  7. CHU Bordeaux, Hopital Haut-Leveque, Pessac, France

    Edouard Forcade

  8. Hospital Universitario de Salamanca (Spain), IBSAL, CIBERONC. Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca, Spain

    Lucía López-Corral

  9. Royal Marsden Hospital, London, UK

    Emma Nicholson

  10. Universita Cattolica S. Cuore, Rome, Italy

    Eugenio Galli

  11. University Hospital Schleswig-Holstein, Kiel, Germany

    Friedrich Stölzel

  12. Universitaet Tuebingen, Tuebingen, Germany

    Wolfgang Bethge

  13. University Medical Center Mainz, Mainz, Germany

    Eva Maria Wagner-Drouet

  14. EBMT Leiden Study Unit, Leiden, The Netherlands

    Jorinde D. Hoogenboom

  15. Karolinska University Hospital, Stockholm, Sweden

    Stephan Mielke

  16. Département d’Oncologie, Service d’Hématologie et Service d’Immuno-Oncologie, CHUV Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

    Caroline Arber

  17. Département d’Oncologie, Service d’Hématologie, Geneva, Switzerland

    Federico Simonetta

  18. Institut Paoli-Calmettes Comprehensive Cancer Centre and Module Biothérapies du Centre d’Investigations Cliniques de Marseille, INSERM-Aix-Marseille Université-AP-HM-IPC, CBT-1409, Marseille, France

    Christian Chabannon

  19. University Medical Center Utrecht, Utrecht, The Netherlands

    Jürgen Kuball

  20. San Raffaele Scientific Institute, Hematology and Bone Marrow Transplantation Unit, Milan, Italy

    Annalisa Ruggeri

  21. Sorbonne Université, Centre de Recherche Saint-Antoine INSERM UMRs938, Paris, France

    Florent Malard

  22. Service d’Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France

    Florent Malard

Authors
  1. Urban Novak
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Contributions

UN was PI of the study, conceptualized study design the survey and data collection. UN provided the study synopsis and the survey form. JEM performed the statistical analysis. MD, CS, LG, IYA, RR, EF, LLC, EN, EG, FS, WB, EMWD, SM, CA, FS were the PIs of the centers mainly involved in the survey and performed data-collection at the center level. JDH performed data management, implemented the online SurveyMonkey tool, and coordinated the study at the EBMT level. CC, JK, AR and FM supervised the study, interpreted the data analysis and gave important intellectual inputs. CC, JK, AR edited the manuscript. FM wrote the manuscript and designed the figures. CTIWP data management team takes the responsibility for the integrity and accuracy of the data presented. All authors reviewed and approved the final version of this manuscript.

Corresponding author

Correspondence to Florent Malard.

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Competing interests

FS: travel Support from Janssen, medac; honoraria from medac, GWT, Abbvie, Servier, Pierre Fabre; research funding from medac, Servier. CA: institutional consulting fees through CHUV from Gilead, Janssen, Celgene/ BMS; institutional sponsored travel through CHUV from Gilead; institutional licensing fees and royalties through previous institution Baylor College of Medicine from Immatics; patents and provisional patent applications in the field of engineered T cell therapies. FS: institutional consulting fees from BMS/Celgene, Incyte, Kite/Gilead; speaker fees from Kite/Gilead, Incyte; travel support from Kite/Gilead, Novartis, AstraZeneca, Neovii, Janssen; research funding from Kite/Gilead, Novartis, BMS/Celgene. CC: Institutional / personal honoraria and travel funding from BMS, Janssen, Jazz, Kite / Gilead, Miltenyi biotec, Novartis. JK: research support from Novartis, Miltenyi Biotech, Gadeta. Florent Malard: honoraria from BMS, Therakos/Mallinckrodt, Sanofi, JAZZ Pharmaceuticals, Gilead, Novartis, AstraZeneca and MSD, all outside the submitted work. The other authors declare no competing financial interests.

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Novak, U., Mooyaart, J.E., Daskalakis, M. et al. Choice of commercially available CAR-T cell products for r/r DLBCL & PMBCL in Europe: a survey on behalf of the cellular therapy & immunobiology working party (CTIWP) of the EBMT. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02401-4

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  • DOI: https://doi.org/10.1038/s41409-024-02401-4

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