Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: The presence of anti-human leukocyte antigen (HLA) antibodies in lung transplant candidates leads to increased wait list times and antibody-mediated rejection (AMR) post-transplant. We describe the efficacy and safety of a multimodal desensitization protocol to reduce antibody burden in sensitized patients awaiting lung transplantation.
*Methods: From 2014-present, sensitized lung transplant candidates underwent desensitization with a 16-day cycle of 6 doses of carfilzomib, 8 sessions of plasmapheresis, and 8 doses of IVIG. The primary outcome was reduction in Class I and II calculated panel reactive antibodies (cPRA), using Luminex single-antigen bead IgG (Mean Fluorescent Intensity (MFI)>2000, IgG-cPRA) and C1q (MFI>500, C1q-cPRA) assays. For transplanted patients, clinical outcomes and survival were described.
*Results: Eight patients underwent 1-3 cycles of the protocol. Seven patients completed at least 1 cycle of therapy, while 1 died during therapy. Change in cPRA is shown in Table 1 for all patients who completed at least 1 cycle. Decline in Class I cPRA was observed in 4/6 patients with baseline Class I antibodies. Class II cPRA declined in 5/7 patients with baseline Class II antibodies. Three patients had Class I C1q+ antibodies, and all 3 saw a decline in Class I C1q+ cPRA after treatment. Four patients were successfully transplanted. The median time from protocol completion to transplant was 32 days. Of the 4 patients who did not proceed to transplant, 1 died during desensitization, and the other 3 died at 12, 168, and 202 days post-treatment, all from respiratory failure. Three patients experienced acute kidney injury and 3 experienced cytopenias. No significant changes in median pre- and post-desensitization serum creatinine or white blood cell count were seen. At 1-year follow up, all 4 transplanted patients were alive, with 1 patient experiencing an episode of antibody-mediated rejection.
*Conclusions: In broadly sensitized lung transplant candidates, desensitization protocol with carfilzomib, plasmapheresis, and IVIG decreased IgG-cPRA, was well tolerated, and allowed 50% of patients to proceed to transplantation.
|Patient||Class I cPRA pre-treatment||Class I cPRA post-treatment||Class II cPRA pre-treatment||Class II cPRA post-treatment|
To cite this abstract in AMA style:Fredrick S, Iasella C, Moore C, Mangiola M, Xu Q, Ensor C, Riciutti D, LaFratte C, Sanchez P, Morrell M, McDyer J, Zeevi A. Outcomes of a Pre-Transplant Desensitization Protocol with Carfilzomib, Plasmapheresis, and IVIG for Broadly Sensitized Lung Transplant Candidates: A Case Series [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/outcomes-of-a-pre-transplant-desensitization-protocol-with-carfilzomib-plasmapheresis-and-ivig-for-broadly-sensitized-lung-transplant-candidates-a-case-series/. Accessed May 7, 2021.
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