Long Term Follow-Up of a Phase 2 Clinical Trial to Induce Tolerance in Living Donor Kidney Transplant Recipients
1Feinberg School of Medicine, Northwestern University, Chicago, IL, 2University of Illinois Chicago, Chicago, IL, 3Northwestern University, Chicago, IL, 4Comprehensive Transplant Center, Northwestern University, Chicago, IL, 5Department of Surgery, Duke University Medical Center, Durham, NC, 6Adult Blood and Marrow Transplant Program, Duke University Medical Center, Durham, NC, 7Talaris Therapeutics Inc, Louisville, KY
Meeting: 2022 American Transplant Congress
Abstract number: 409
Keywords: Bone marrow transplantation, Kidney, Kidney transplantation, Tolerance
Topic: Clinical Science » Kidney » 38 - Kidney Immunosuppression: Novel Regimens and Drug Minimization
Session Information
Session Name: Kidney Immunosuppression
Session Type: Rapid Fire Oral Abstract
Date: Tuesday, June 7, 2022
Session Time: 3:30pm-5:00pm
Presentation Time: 3:30pm-3:40pm
Location: Hynes Room 302
*Purpose: 37 subjects were transplanted in a phase 2 protocol based upon tolerogenic CD8+/TCR-facilitating cells (FCR001) to induce tolerance in recipients of living donor kidney allografts (KTx).
*Methods: Recipients were conditioned with fludarabine (30mg/m2/dose, days -5, -4, -3), cyclophosphamide (50mg/kg/dose, day-3 and+3), 200 cGy TBI (day-1) followed by KTx (day 0). A G-CSF mobilized product was apheresed from the donor, processed to remove graft-versus-host disease (GVHD)-producing cells yet retain CD34+ cells and FC, and cryopreserved until administration day +1 post-KTx. Follow up is 60 – 154 months. Pts ranged in age from 18-64 yrs and were 6/6 HLA matched related to 0/6 matched unrelated. MMF and tacrolimus immunosuppression (IS) was weaned and discontinued at 1 yr if post-Tx chimerism, normal kidney function and normal KTx biopsy were noted.
*Results: Durable chimerism allowing for full IS withdrawal developed in 26 pts (time off IS 48- 136 months); the majority (23/26) showed full (>95%) donor whole blood/T cell chimerism. 6 subjects have been IS free for > 10 years. Transient chimerism was seen in 8 pts. All stable chimeric subjects retained chimerism after removal of IS and remain rejection-free. Long term chimeric subjects off IS have no evidence of immune defect: they show robust T, B, and NK cell reconstitution, can be safely vaccinated and develop protective immunity. Transiently chimeric pts resumed endogenous hematopoiesis and were maintained on low-dose IS. There were two cases of GVHD. 1 subject exhibited grade 1-2 acute GI GVHD that responded to corticosteroids, followed by mild chronic GVHD. The second pt presented late and died of treatment resistant GI GVHD with CMV 11 months post-Tx. There have been three graft losses, related to infections in subjects on IS. There have been three subject deaths. Overall patient survival is 89.2% and death censored graft survival 91.9%. Tolerant FCR001 subjects have significantly better kidney function than comparable KTx on SOC IS. Hypertension and hyperlipidemia medication use is more common in SOC than tolerant FCR001 pts.
*Conclusions: High levels of durable chimerism and tolerance with a low (5.5%) incidence of GVHD has been achieved in mismatched recipients of KTx. There are significant long-term medical benefits to establishing tolerance in KTx recipients using the FCR001 approach.
To cite this abstract in AMA style:
Leventhal J, Galvin J, Mathew J, Gallon L, Belshe D, Gibson M, Ravindra K, Horwitz M, Ildstad S. Long Term Follow-Up of a Phase 2 Clinical Trial to Induce Tolerance in Living Donor Kidney Transplant Recipients [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/long-term-follow-up-of-a-phase-2-clinical-trial-to-induce-tolerance-in-living-donor-kidney-transplant-recipients/. Accessed May 17, 2025.« Back to 2022 American Transplant Congress