Calcineurin Inhibitor–Free, mTOR‐Based Immunosuppression in Chimeric Antigen Receptor T‐Cell Therapy for Post‐Transplant Lymphoproliferative Disorder
Maria Mappoura, Yara Hajj Younes, Sisi Wang, Kadiatou Baldet, Carmen De Ramon Ortiz, Sarah Morin, Stavroula Marouridi‐Levrat, Amandine Pradier, Astrid Melotti, Pragallabh Purwar, Chiara Bernardi, Liza Ho, Kristof Egervari, Julie Ducreux, Thomas Longval, Francesco Bertoni, Yves Chalandon, Fadi Haidar, Sophie de Seigneux, Jean Villard, Valérie Olivier, Federico SimonettaABSTRACT
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.