*Purpose: Late antibody-mediated rejection (ABMR) is a major cause of transplant failure. Potential therapeutic targets are plasma cells (PC) and natural killer (NK) cells expressing high levels of CD38. Here we report the use of CD38 monoclonal antibody daratumumab in a kidney allograft recipient diagnosed with multiple myeloma and HLA class II donor-specific (DSA)-positive chronic active ABMR 13 years after transplantation.

*Methods: Daratumumab was given on a compassionate use basis (intravenous application of 16 mg/kg weekly for 8 weeks, every other week for 16 weeks and every 4 weeks thereafter). Biopsies were evaluated using the Banff 2017 scheme, including gene expression analysis (Molecular Microscope Diagnostic System). For immune cell phenotyping standardized pre-formulated dry antibody panels (DuraClone system) and for HLA antibody detection single antigen bead assays were used.

*Results: Daratumumab led to persistent PC depletion in the bone marrow and blood, and substantially decreased circulating and allograft infiltrating NK cells. At the same time, DSA in serum disappeared, and in vitro alloantibody production by PC enriched from bone marrow aspirates was abrogated. A 3-month follow-up biopsy revealed a resolution of microcirculation inflammation (g+ptc: 3 to 0) and molecular ABMR activity (ABMR score: 0.79 to <0.1). The same biopsy showed de novo borderline rejection, but without molecular patterns of T cell-mediated rejection. Over an observation period of 15 months, graft function stabilized and urinary protein excretion decreased.

*Conclusions: Our results may encourage the design of future trials to clarify the role of this innovative treatment concept in organ transplantation.

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