Preformed T‐cell alloimmunity and HLA eplet mismatch to guide immunosuppression minimization with Tacrolimus monotherapy in Kidney Transplantation. Results of the CELLIMIN trial

Personalizing immunosuppression is a major objective in transplantation. Transplant recipients are heterogenous regarding their immunological memory and primary alloimmune susceptibility. This biomarker-guided trial investigated whether in low immunological-risk kidney transplants without pretransplant DSA and donor-specific T cells assessed by a standardized IFN-γ ELISPOT, low immunosuppression (LI) with tacrolimus monotherapy would be non-inferior regarding 6-month BPAR than tacrolimus-based standard-of-care (SOC). Due to low recruitment rates, the trial was terminated when 167 patients were enrolled. ELISPOT negatives (E-) were randomized to LI(n=53) or SOC(n=48), E+ received the same SOC. Six and 12-month BPAR was higher among LI than SOC/E- (4/35[13%] vs 1/43[2%], p=0.15 and 12/48[25%] vs 6/53[11.3%], p=0.073, respectively). E+ patients showed similarly high BPAR rates than LI at 6 and 12 months (12/66[18%] and 13/66[20%], respectively). These differences were stronger in per-protocol analyses. Post-hoc analysis revealed that poor class-II eplet matching, especially DQ, discriminated E- patients, notably E-/LI, developing BPAR (4/28[14%] low-risk vs 8/20[40%] high-risk, p=0.043). Eplet mismatch also predicted anti-class-I (p=0.05) and anti-DQ (p=0.001) de novo DSA. Adverse events were similar, but E-/LI developed fewer viral infections, particularly Polyoma-virus associated nephropathy (p=0.021). Preformed T-cell alloreactivity and HLA eplet mismatch assessment may refine current baseline immune-risk stratification and guide immunosuppression decision-making in kidney transplantation.