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Kidney Week

Abstract: PO2040

Preserved Kidney Allograft Function and Unique Urinary Biomarker Profiles in Living Donor Kidney Transplant (LDKT) Patients Tolerized with an Investigational Allo-Hematopoietic Stem Cell Transplantation Therapy

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Leventhal, Joseph, Northwestern University, Evanston, Illinois, United States
  • Galvin, John Patrick, Northwestern University, Evanston, Illinois, United States
  • Ison, Michael G., Northwestern University, Evanston, Illinois, United States
  • Lee, John Richard, Weill Cornell Medicine, New York, New York, United States
  • Mathew, James M., Northwestern University, Evanston, Illinois, United States
  • Gallon, Lorenzo G., Northwestern University, Evanston, Illinois, United States
  • Gibson, Meg, Northwestern University, Evanston, Illinois, United States
  • Belshe, Dianne Stare, Northwestern University, Evanston, Illinois, United States
  • Tollerud, David, Talaris Therapeutics, Louisville, Kentucky, United States
  • Suthanthiran, Manikkam, Weill Cornell Medicine, New York, New York, United States
  • Ildstad, Suzanne, Talaris Therapeutics, Louisville, Kentucky, United States
Background

We previously reported that 37 patients were transplanted in an open-label, single-arm phase 2 protocol to induce immune tolerance in LDKT recipients.

Methods

The protocol was based upon tolerogenic CD8+/TCR- facilitating cells (FCR001), nonmyeloablative conditioning and enrollment agnostic to the degree of HLA mismatch. Tacrolimus/MMF based immunosuppression (IS) was weaned and discontinued at one year if durable chimerism and normal kidney function and transplant biopsy were confirmed.

Results

Durable chimerism enabled complete withdrawal of IS in 26/37 patients. Comparison of clinical outcomes in FCR001 and a SOC cohort showed comparable patient survival and graft survival at two, three and five years. Cardiovascular medication usage was more frequent in SOC than in tolerant FCR001 subjects for hypertension (83% vs 18%) and hyperlipidemia (43% vs 9%). Graft function (eGFR) was better and more stable for the FCR001 cohort compared to SOC, with the difference due to patients with durable chimerism and off IS.
Urinary cell mRNA profiling of a subgroup of FCR001 patients identified a potential signature of tolerance, characterized by increased levels of CTLA4 mRNA, and a higher ratio of CTLA4 mRNA to mRNA for granzyme B and perforin mRNA. If validated, such a signature of tolerance might help identify kidney transplant patients in whom reduction of IS drugs might be safely undertaken. To date, we have accumulated approximately 235 patient-years of exposure to FCR001 in LDKT, and the safety profile is consistent with that expected if a patient were to receive both a kidney transplant and an allo-HSCT with nonmyeloablative conditioning.

Conclusion

We continue to monitor the patients in the Phase 2 trial for long-term safety and durability of immune tolerance and graft function. We are currently enrolling patients in FREEDOM-1, a randomized, controlled, open-label Phase 3 trial in the US in adult LDKT recipients.

eGFRMonth 1Year 1Year 2Year 3Year 4Year 5
Chimeric off IS58.860.665.465.064.366.1
ITT55.060.563.763.762.962.6
SOC 58.958.155.451.5 

Funding

  • Commercial Support