A multicenter registry study of the CD38 antibody daratumumab for the treatment of microvascular inflammation following kidney transplantation

Introduction Microvascular inflammation (MVI) on kidney biopsy is associated with reduced graft survival following kidney transplantation (KT). CD38- targeting regimens, including the monoclonal antibody daratumumab, have recently emerged as a promising therapeutic strategy to counteract MVI and stabilize graft function. Methods Here, we retrospectively collected data on eGFR, albuminuria, kidney allograft pathology, donor specific antibodies (DSA) and donor-derived cell-free DNA (dd-cfDNA) levels from 70 KT patients both prior to and after initiation of daratumumab treatment. Safety signals were also documented. Results The study cohort consisted of 59 patients diagnosed with antibody mediated rejection (AMR) and 11 patients showing DSA- and C4d-negative MVI. Median time between transplantation and diagnosis of MVI was 36 months. Daratumumab treatment was initiated at a median of 1.6 months following diagnosis of MVI. A mixed linear model showed stabilization of eGFR from -1.6 ml/min/1.73m 2 /month in the year prior to the diagnosis of MVI to +0.3 83 ml/min/1.73m 2 /month after starting daratumumab. Six patients lost their graft during follow-up. Median albuminuria and dd-cfDNA levels decreased early during treatment, whereas the effect on DSA was heterogeneous. Both the number of doses and treatment duration had no measurable impact on outcome. Conclusions Our preliminary data suggests efficacy of daratumumab in stabilizing kidney function in KT recipients with MVI.