Systematic Review of Immunosuppression After Chimeric Antigen Receptor T-Cell Therapy for Posttransplant Lymphoproliferative Disorder

TL;DR

This paper reviews how immunosuppression is managed after CAR T-cell therapy for posttransplant lymphoproliferative disorder in organ transplant patients.

Contribution

The study systematically reviews the lack of consensus on optimal immunosuppressive strategies post-CAR T-cell therapy for PTLD.

Findings

There is substantial variability in immunosuppressive management before and after CAR T-cell infusion.

No single immunosuppression regimen has been shown to be clearly superior due to limited data.

An individualized approach is needed, considering factors like CAR T-cell persistence and B-cell depletion.

Abstract

The use of chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory posttransplant lymphoproliferative disorder (PTLD) in solid organ transplant recipients is a rapidly evolving frontier in immunotherapy and transplantation. In this context, clinicians must carefully balance the competing risks of allograft rejection, the potential for maintenance immunosuppression to diminish CAR T-cell efficacy and treatment response, alongside an increased infection risk. Given the heterogeneous nature of PTLD and the scarcity of clinical trial data in this specific population, there is currently no established consensus regarding the optimal maintenance immunosuppressive strategy post–CAR T-cell therapy.

To address this gap, we conducted a systematic review of published data pertaining to CAR T-cell therapy and PTLD after solid organ transplantation.

Our findings reveal substantial variability in immunosuppressive management before and after CAR T-cell infusion, including the withholding of immunosuppression, or the use of single agent or combinations of corticosteroids, calcineurin inhibitors (CNIs), antimetabolites, or mammalian target of rapamycin (mTOR) inhibitors. Given the limited data to date, balancing these competing risks is challenging, and no single immunosuppression regimen has emerged as clearly superior.

Our review underscores the necessity of an individualized approach to these patients that accounts for factors such as CAR T-cell persistence and prolonged B-cell depletion, and highlights the need for further research on this clinical scenario.

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