Calcineurin Inhibitor–Free, mTOR‐Based Immunosuppression in Chimeric Antigen Receptor T‐Cell Therapy for Post‐Transplant Lymphoproliferative Disorder
ABSTRACT Introduction Relapsed/refractory post‐transplant lymphoproliferative disorder (PTLD) remains a challenging complication after solid organ transplantation (SOT), requiring complex balancing of immune‐suppressive therapy (IST) and lymphoma‐directed therapies. Methods We report the case of a 40‐year‐old female kidney‐pancreas transplant recipient with relapsing monomorphic PTLD treated with CD19‐chimeric antigen receptor (CAR) T cells therapy (axicabtagene ciloleucel). Results Tacrolimus discontinuation and immunosuppression with everolimus and corticosteroids permitted robust CAR T‐cell expansion, complete lymphoma remission, and preservation of graft function. In vitro studies showed that tacrolimus inhibited CAR T‐cell function, while everolimus preserved it, supporting the use of mTOR‐based, calcineurin‐inhibitor‐free IST during CAR T‐cell therapy in SOT recipients. Conclusion mTOR‐based, calcineurin inhibitor–free immunosuppression can preserve CAR T‐cell function and enable effective therapy in SOT recipients with PTLD.
Authors
- Sophie de Seigneux (ORCID: https://orcid.org/0000-0002-4243-366X)
- Maria Mappoura (ORCID: https://orcid.org/0000-0001-9499-7865)
- Kadiatou Baldet
- Amandine Pradier
- Liza K.F. Ho
- Sarah Morin
- Federico Simonetta (ORCID: https://orcid.org/0000-0002-5928-9836)
- Fadi Haidar (ORCID: https://orcid.org/0000-0002-8133-1105)
- Astrid Melotti
- Valérie Olivier (ORCID: https://orcid.org/0000-0001-9308-4853)
- Kristof Levente Egervari (ORCID: https://orcid.org/0000-0001-6763-9069)
- Chiara Bernardi (ORCID: https://orcid.org/0000-0001-5118-5402)
- Francesco Bertoni (ORCID: https://orcid.org/0000-0001-5637-8983)
- Thomas Longval (ORCID: https://orcid.org/0000-0002-0254-1519)
- Yves Chalandon (ORCID: https://orcid.org/0000-0001-9341-8104)
- Jean Villard (ORCID: https://orcid.org/0000-0003-2667-7506)
- Julie Ducreux
- Pragallabh Purwar
- Sisi Wang
- Yara Hajj Younes
- Stavroula Marouridi‐Levrat
- Carmen De Ramon Ortiz
Institutions
- University of Geneva (CH)
- Ente Ospedaliero Cantonale (CH)
- Institute of Oncology Research (CH)
- University Hospital of Geneva (CH)
- Istituto Oncologico della Svizzera Italiana (CH)
- Università della Svizzera italiana (CH)
Publication Details
- Journal
- eJHaem
- Published
- 2026-10-28
- DOI
- https://doi.org/10.1002/jha2.70437
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00