*Purpose: Antibody-Mediated Rejection (ABMR) is a severe form of rejection mediated by B-cells, plasma cells and antibodies. The consequences to the patients with ABMR are often severe with high rates of graft loss and poor patient survival. Daratumumab (anti-CD38) is a humanized monoclonal with specificity for plasma cells and other immune cells designed for treatment of multiple myeloma. Here, we present a case of daratumumab used for treatment of standard of care(SOC) resistant ABMR.

*Methods: Patient is a 33 y.o. highly-HLA sensitized female who developed severe ABMR post-HLAi transplant, resistant to treatment with PLEX+IVIg+Rituximab and eculizumab. After consent, the patient was treated with anti-CD38 (16mg/kg weekly X 4). Prior to and at completion of treatment, luminex-HLA antibodies HLA (class I &II) and immune cell phenotyping (T_fh, T_reg, B_naive, plasmablast and plasma cells) were determined. A biopsy was also performed pre and post-daratumumab treatment.

*Results: Pre & post-transplant HLA antibody MFIs are shown in Figures 1a and b. Briefly, HLA class I antibodies were reduced 55% (p= 0.03) while class II were reduced 33% (p=NS). DSAs DQ7 were reduced from >17,500 -> 5000 MFI. Immune cell phenotyping showed complete eradication of CD38+ cells including B_regs, B_memory, plasmablast, and plasma cells. However, marked increases in total CD4+, T_fh and T_reg were seen in peripheral blood. Repeat biopsy performed at completion of daratumumab treatment showed no evidence of ABMR (see Figure 1c). However, the patient had developed severe cell-mediated rejection(CMR). Assessment of renal function showed only marginal improvements.

*Conclusions: Daratumumab was well tolerated with minimal AEs noted. The treatment regimen showed significant reductions in circulating HLA class I and good reductions in class II with resolution of ABMR. However, elimination of B_regs may have incited CMR. Complete elimination of features of ABMR may also be aided by anti-CD38 depletion of CD38+ NK cells, thus restricting antibody-dependent cellular cytotoxicity(ADCC).

« Back to 2019 American Transplant Congress