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CD19 CAR-T therapy in solid organ transplant recipients: case report and systematic review

Bone Marrow Transplantation volume 58, pages 353–359 (2023)Cite this article

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Abstract

Post-transplant lymphoproliferative disorder (PTLD) is a leading cause of cancer death in solid organ transplant recipients (SOTRs). Relapsed or refractory (R/R) PTLD portends a high risk of death and effective management is not well established. CD19-targeted CAR-T cell therapy has been utilized, but the risks and benefits are unknown. We report the first case of diffuse large B-cell lymphoma (DLBCL) PTLD treated with lisocabtagene maraleucel and present a systematic literature review of SOTRs with PTLD treated with CD19 CAR-T therapy. Our patient achieved a complete response (CR) with limited toxicity but experienced a CD19+ relapse 8 months after infusion despite CAR-T persistence. Literature review revealed 14 DLBCL and 2 Burkitt lymphoma PTLD cases treated with CD19 CAR-T cells. Kidney (n = 12), liver (n = 2), heart (n = 2), and pancreas after kidney (n = 1) transplant recipients were analyzed. The objective response rate (ORR) was 82.4% (14/17), with 58.5% (10/17) CRs and a 6.5-month median duration of response. Among kidney transplant recipients, the ORR was 91.7% (11/12). Allograft rejection occurred in 23.5% (4/17). No graft failure occurred. Our analysis suggests that CD19 CAR-T therapy offers short-term effectiveness and manageable toxicity in SOTRs with R/R PTLD. Further investigation through larger datasets and prospective study is needed.

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Fig. 1: Lab parameters of our patient relative to lisocabtagene maraleucel CAR-T infusion.
Fig. 2: Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram of study selection.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by an institutional training grant from the National Heart, Lung, and Blood Institute (T32 HL007093). We thank Drs. Alberto Mussetti and Edoardo Melilli (Catalan Institute of Oncology) for providing additional information pertaining to their case report.

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Authors and Affiliations

  1. University of Washington, Seattle, WA, USA

    Andrew J. Portuguese, Jordan Gauthier, Scott S. Tykodi, Evan T. Hall, Alexandre V. Hirayama, Cecilia C. S. Yeung & Christopher D. Blosser

  2. Fred Hutchinson Cancer Center, Seattle, WA, USA

    Andrew J. Portuguese, Jordan Gauthier, Scott S. Tykodi, Evan T. Hall, Alexandre V. Hirayama & Cecilia C. S. Yeung

  3. Seattle Children’s Hospital, Seattle, WA, USA

    Christopher D. Blosser

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Contributions

AP and CB performed the literature review. AP acquired data, analyzed and interpreted data and drafted the manuscript. ST, JG, EH, and CB revised the manuscript critically for important intellectual content. AH and CY performed research sample testing and edited the manuscript. CB conceived the study, analyzed and interpreted data, and provided critical oversight.

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Correspondence to Andrew J. Portuguese.

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Competing interests

AP has disclosed receiving support from an institutional training grant from the National Heart, Lung, and Blood Institute (T32 HL007093). JG has disclosed receiving research funding from Sobi, Juno Therapeutics, and Celgene; receiving consulting fees from Eusapharma, JMP, Larvol, and Multerra Bio; and serving on advisory boards for Legend Biotech and Janssen. ST has disclosed receiving grant/research support from AVEO Oncology, Bristol-Myers Squibb, Merck & Co., Genentech, Pfizer, Nektar Therapeutics, Exelixis, and Jounce Therapeutics; receiving consulting fees from PLS Group Services, Exelixis, Merck & Co., Bristol-Myers Squibb, and Intellisphere LLC; serving on an advisory board for Merck & Co., Exelixis, and Bristol-Myers Squibb; receiving honoraria from Natera and General Dynamics Information Technology; and serving as a consultant for Targeted Oncology. CB has disclosed serving as a consultant for Natera and Sandoz, and participating in research funded by Natera. EH has disclosed serving as a principal investigator for Neoleukin Therapeutics, ImCheck Therapeutics, Checkpoint Pharmaceuticals, and Nektar. AH has disclosed receiving research funding from Juno Therapeutics, and NanoString Technologies; receiving honoraria from Bristol-Myers Squibb and Novartis. CY has disclosed receiving grant/research support from Pfizer, Sensei Biotherapeutics, Exicure, Incyte, Signal One, Lonza, OBI; receiving consulting fees from Twinstrands; serving on an advisory board for Merck & Co., and Eli-Lily. The remaining authors have disclosed no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.

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Portuguese, A.J., Gauthier, J., Tykodi, S.S. et al. CD19 CAR-T therapy in solid organ transplant recipients: case report and systematic review. Bone Marrow Transplant 58, 353–359 (2023). https://doi.org/10.1038/s41409-022-01907-z

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  • DOI: https://doi.org/10.1038/s41409-022-01907-z

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