Immune tolerance via FCR001 cell therapy compared with maintenance immunosuppression for kidney transplantation: Real-world evidence analysis of safety and efficacy

Clin Transplant. 2023 Nov;37(11):e15074. doi: 10.1111/ctr.15074. Epub 2023 Aug 3.

Abstract

While kidney transplantation (KTx) has traditionally required lifelong immunosuppression, an investigational stem cell therapy, FCR001, has been demonstrated to induce tolerance and eliminate the need for immunosuppression through the establishment of persistent mixed chimerism in a phase 2 clinical study. Real-world evidence (RWE) methods were employed to compare the safety and efficacy of non-myeloablative conditioning with FCR001 with standard of care [SOC] immunosuppression in a retrospective single-center analysis of outcomes among propensity score matched living-donor KTx receiving SOC (n = 144) or FCR001 (n = 36). Among the FCR001 recipients, 26 (72%) developed persistent chimerism allowing durable elimination of all immunosuppression. There was no significant difference in the composite primary endpoint (biopsy-proven acute rejection [BPAR], graft loss, or death) at 60 months (FCR001 27.8%, n = 10 and SOC 28.5%, n = 41; p = .9). FCR001 recipients demonstrated superior kidney function at 5 years (estimated glomerular filtration rate [eGFR] [mean ± standard deviation]: 64.1 ± 15.3) compared to SOC (51.7 ± 18.8; p = .02). At 5 years, FCR001 recipients experienced fewer complications including new-onset diabetes post-transplant, although two patients developed graft versus host disease. In conclusion, RWE demonstrated that KTx combined with non-myeloablative conditioning and FCR001 resulting in superior kidney function without increasing the risk of rejection, graft loss, or death among patients off immunosuppression.

Keywords: immunosuppressive regimens; kidney transplantation: living donor; tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Graft Rejection / etiology
  • Graft Rejection / prevention & control
  • Graft vs Host Disease*
  • Humans
  • Immune Tolerance
  • Immunosuppression Therapy
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation* / adverse effects
  • Retrospective Studies

Substances

  • Immunosuppressive Agents