Scientific Poster Session IV - Case Reports

Abstract

Antibody-mediated rejection (ABMR) leads to generation of plasma cells and antibodies, increasing the risk of graft failure. Emerging data with proteasome inhibitors (PIs) show potential in ABMR through plasma cell apoptosis. Differences exist between the available agents (bortezomib/carfilzomib) in side effect profile and proteasome binding duration. We report the first use of carfilzomib for ABMR in a multivisceral transplant (MVTx) recipient.

Case:

A 21-year-old MVTx recipient presented with a chief complaint of nausea, vomiting, and diarrhea. They had a history of gastroschisis requiring intestinal transplant (ITx) in 2010 (failed from rejection) and underwent MVTx (liver/pancreas/intestine) in 2016. Intestinal biopsies revealed cellular rejection and presence of class II donor-specific antibodies (DSA), which prompted treatment with methylprednisolone, anti-thymocyte globulin, plasmapheresis, intravenous immunoglobulin, and two doses of bortezomib. A month later they were still unable to tolerate enteral feeds and biopsy re-demonstrated ABMR with newly positive C4d staining and increased DSAs. Plasmapheresis and intravenous immunoglobulin were restarted with the addition of carfilzomib for five doses. After completion, DSAs down-trended and biopsy showed no rejection and negative C4d staining. Over the following months, DSAs rebounded and biopsy-proven rejection returned, ultimately leading to graft failure and patient death.

Discussion:

This report details the novel use of carfilzomib for ABMR in MVTx. Data with carfilzomib is limited to two case series in lung transplant ABMR, with inconclusive findings on graft function and antibody response. For MVTx recipients, there is only one published use of a PI (bortezomib) for early ABMR in ITx that resulted in long-term DSA suppression, however this was not seen in our patient with late ABMR. We hypothesize that the timing of ABMR diagnosis may play a role in PI efficacy.

Conclusion:

Carfilzomib may be used in multimodal treatment of ABMR in MVTx with short-term positive results. More data is needed for late ABMR after MVTx.

Presenting Author

Authors