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Out of specification Tisagenlecleucel is associated with outcomes comparable to standard of care product in relapsed or refractory diffuse large B-cell lymphoma

Bone Marrow Transplantation volume 59, pages 569–571 (2024)Cite this article

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Chimeric antigen receptors (CAR) T-cell therapy has revolutionized the treatment of relapsed/refractory (r/r) Diffuse Large B Cell Lymphoma (DLBCL). Tisagenlecleucel (Tisa-cel) was approved as a third-line treatment in this setting after the results from the JULIET trial showed an overall response rate (ORR) of 52%, a complete response rate (CR) of 40% and median overall survival (OS) of 12 months [1]. The update with long-term data indicates that approximately 30% of the patients show a durable response [2].

Behind the success, there is a complex manufacturing process. Commercial products undergo strict tests to guarantee the quality criteria. Concerning Tisa-cel, quality attributes consider safety, purity, quantity and potency with several parameters. A final product with all the quality criteria is acknowledged as “standard-of-care” (SOC), while the ones not fitting the benchmark are considered “out-of-specification” (OOS) [3]. In this case physicians can take the responsibility to infuse the OOS product, according to EMA guidelines [4].

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Fig. 1: Kaplan–Meier curves.

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Authors and Affiliations

  1. IRCCS Humanitas Research Hospital, Transplantation Unit Department of Oncology and Haematology, Rozzano, Milan, Italy

    Chiara De Philippis, Cristina Zucchinetti, Daniele Mannina, Flavio Pistolese, Armando Santoro & Stefania Bramanti

  2. Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan, Italy

    Cristina Zucchinetti, Flavio Pistolese & Armando Santoro

  3. Hematology and Bone Marrow Transplant Unit, Department of Engineering for Innovative Medicine, Section of Biomedicine of Innovation, University of Verona, Verona, Italy

    Mauro Krampera

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

    Pier Luigi Zinzani

  5. Division of Hematology and Stem Cell Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Milano, Milano, Italy

    Annalisa Chiappella

  6. Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

    Alice di Rocco

  7. Azienda Ospedaliero-Universitaria Pisana, UO Ematologia, Pisa, Italy

    Enrico Orcioulo

  8. Hematology Unit, San Bortolo Hospital, AULSS 8 Berica, Vicenza, Italy

    Maria Chiara Tisi

  9. IRCCS Humanitas Research Hospital- Humanitas Cancer Center, Biostatistic Unit, Rozzano, Milan, Italy

    Laura Giordano

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  1. Chiara De Philippis
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Contributions

CDP, CZ and DM designed research and wrote the paper. PLZ, MK, AC, ADR, EO, MCT and FP have collected the data. LG performed the statistical analyses. AS and SB designed research and reviewed the paper.

Corresponding author

Correspondence to Armando Santoro.

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Competing interests

AC: Advisory Board: Ideogen, Roche, Takeda. Speakers’ Bureau: Astrazeneca, Gilead-Sciences, Janssen-Cilag, Novartis. PLZ: Consulting or Advisory Role: Sanofi, Verastem, Celltrion, Gilead Sciences, Janssen-Cilag, Bristol-Myers Squibb, Servier, Sandoz, MSD, Immune Design, Celgene, Portola Pharmaceuticals, Roche, EUSA Pharma, Kyowa Hakko Kirin. Speakers’ Bureau: Verastem, Celltrion, Gilead Sciences, Janssen-Cilag, Bristol-Myers Squibb, Servier, Sandoz, MSD, Immune Design, Celgene, Portola Pharmaceuticals, Roche, EUSA Pharma, Kyowa Hakko Kirin. AS: Consulting or Advisory Role: Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD. Speakers’ Bureau: Takeda, Roche, AbbVie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis. CDP: Speakers’ Bureau: Novartis, Gilead. DM: Speakers’ Bureau: Novartis, Gilead. SB: Speakers’ Bureau: Novartis, Gilead, Astra-Zeneca, Roche, Kiova, Bristol-Myers-Squibb.

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De Philippis, C., Zucchinetti, C., Mannina, D. et al. Out of specification Tisagenlecleucel is associated with outcomes comparable to standard of care product in relapsed or refractory diffuse large B-cell lymphoma. Bone Marrow Transplant 59, 569–571 (2024). https://doi.org/10.1038/s41409-024-02205-6

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  • DOI: https://doi.org/10.1038/s41409-024-02205-6

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