Searching for the minimum required dose of daratumumab to induce effective plasma cell depletion in antibody-mediated rejection of the kidney graft: a case report

There is no established treatment for late or chronic antibody-mediated rejection of a kidney graft. Rituximab-based treatment is not effective, since long-lived high-affinity plasma cells do not express CD20 and do not depend on previous maturation steps to generate donor-specific antibodies. Conversely, daratumumab, an anti-CD38 monoclonal antibody, directly targets plasma cells, with proven efficacy in multiple myeloma. Early reports in heart and kidney transplantation showed its efficacy in the setting of antibody-mediated rejection or desensitization. However, the dosage to be used was assumed to be the same as in multiple myeloma treatment. We present the case of a patient with late antibody-mediated rejection, resistant to two cycles of rituximab-based therapy, who underwent a cycle of plasma exchange and intravenous gammaglobulins preceded and followed by only 2 doses of daratumumab. Bone marrow aspirate after the cycle demonstrated negativization of CD38 + cells, which was followed by negativization of the donor-specific antibodies and improvement of microinflammation at kidney biopsy. This suggests that the myeloma-like dosage used in previous reports may not be necessary for non-neoplastic diseases like antibody-mediated rejection. We propose a pragmatic approach, based on the assessment of bone marrow plasma cells after treatment, to avoid unnecessary side effects and optimize resources.