Induction of Immune Tolerance in Living Related HLA-Matched Kidney Transplantation: A Phase 3 Randomized Clinical Trial.
Kaufman, D. B., et alAmerican Journal of Transplantation 2025 [record in progress].
Aims
This study aimed to investigate whether the MDR-101, a donor-derived cellular product, was able to induce immune tolerance compared to standard treatment in renal transplant patients.
Interventions
Participants were randomised to either receive MDR-101 or standard immunosuppression.
Participants
30 adult kidney transplant recipients from 2-haplotype human leukocyte antigen (HLA) –matched living siblings.
Outcomes
The primary efficacy endpoint was the proportion of patients that achieved functional immune tolerance. Other outcomes measured were quality of life, adverse events, and renal and metabolic function.
Follow-up
36 months
CET Conclusions
This interesting multicentre randomised study investigated the ability of a dnor stem-cell derived cell therapy product (MDR-101) to induce clinical tolerance in recipients of HLA-matched sibling renal transplants. Recipients received rATG induction and low-dose lymphoid irradiation post-transplant, followed by MDR-101 cell therapy on day 11. During the first-year post-transplant, immunosuppression was gradually withdrawn until tacrolimus was stopped completely at 1 year in patients with evidence of mixed chimerism. 75% of patients (15/20) remained IS-free for 2 years with an acceptable safety profile. Although small (just 30 patients), this is a challenging study to undertake, and the results are impressive. Application is currently limited to 2-haplotype matched siblings, but the ability to deliver therapy post-transplant provides scope to extend to previously transplanted eligible recipients.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT03363945