Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*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 (Tfh, Treg, Bnaive, 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 Bregs, Bmemory, plasmablast, and plasma cells. However, marked increases in total CD4+, Tfh and Treg 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 Bregs 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).
To cite this abstract in AMA style:Jordan SC, Vescio R, Toyoda M, Ammerman N, Huang E, Peng A, Sethi S, Najjar R, Lim K, Vo A. Daratumumab for Treatment of Antibody-Mediated Rejection in a Kidney Transplant Recipient [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/daratumumab-for-treatment-of-antibody-mediated-rejection-in-a-kidney-transplant-recipient/. Accessed May 9, 2021.
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