Induction of immune tolerance in living related human leukocyte antigen-matched kidney transplantation: A phase 3 randomized clinical trial.
Publication/Presentation Date
7-1-2025
Abstract
This phase 3 multicenter, randomized, controlled clinical trial evaluated investigational cellular product (MDR-101) to produce immune tolerance vs standard of care, in kidney transplant recipients. Adult recipients of kidneys from 2-haplotype human leukocyte antigen-matched living siblings were randomized 2:1 to treatment (n = 20) or control (n = 10). The MDR-101 product was from the same kidney donor. Treatment recipients received a nonmyeloablative conditioning protocol with rabbit-antithymocyte globulin and low-dose total lymphoid irradiation (10 fractions). MDR-101 was infused (day 11). Steroids were withdrawn by day 10 and mycophenolate by day 39. Tacrolimus was continued until day 180 and tapered to withdrawal 1-year posttransplant if donor hematopoietic mixed chimerism was ≥5%. Controls received immunosuppression (IS) per institutional standard of care. Twenty recipients received the MDR-101 infusion, and none developed graft versus host disease. Nineteen (95%) successfully discontinued all IS approximately 1 year after kidney transplant. Fifteen (75%) reached the primary study endpoint of IS-free for >2 years. Four resumed IS: 1 with recurrent immunoglobulin A nephropathy; 1 with recurrent immunoglobulin A nephropathy and rejection; 1 with rejection; and 1 with borderline biopsy changes. Kidney transplant recipients receiving MDR-101 achieved donor mixed chimerism and functional immune tolerance for greater than 2 years with no death, graft loss, DSA, or graft versus host disease and demonstrated improved quality of life compared to standard treatment.
Volume
25
Issue
7
First Page
1461
Last Page
1470
ISSN
1600-6143
Published In/Presented At
Kaufman, D. B., Akkina, S. K., Stegall, M. D., Piper, J. B., Gaber, A. O., Asch, W. S., Busque, S., Stites, E., De Vera, M., Srinivas, T. R., Alonso, D., Shah, A., Patel, A., Mai, M. L., Chavin, K. D., DebRoy, M., Jittirat, A., Costa, N., Cooper, M., Vranic, G., … MDR-101-MLK Study Group (2025). Induction of immune tolerance in living related human leukocyte antigen-matched kidney transplantation: A phase 3 randomized clinical trial. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 25(7), 1461–1470. https://doi.org/10.1016/j.ajt.2025.01.044
Disciplines
Medicine and Health Sciences
PubMedID
39922283
Department(s)
Department of Surgery
Document Type
Article