Outcomes of a Pre-Transplant Desensitization Protocol with Carfilzomib, Plasmapheresis, and IVIG for Broadly Sensitized Lung Transplant Candidates: A Case Series
1Department of Pharmacy, UPMC Presbyterian, Pittsburgh, PA, 2University of Pittsburgh School of Pharmacy, Pittsburgh, PA, 3University of Pittsburgh School of Medicine, Pittsburgh, PA, 4Department of Pharmacy, AdventHealth, Orlando, FL
Meeting: 2020 American Transplant Congress
Abstract number: C-304
Keywords: Antibodies, IgG, Plasmapheresis, Sensitization
Session Information
Session Name: Poster Session C: Lung: All Topics
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*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 |
| 1 | 83 | 17 | 80 | 98 |
| 2* | 0 | 0 | 68 | 0 |
| 3* | 87 | 45 | 56 | 0 |
| 4 | 100 | 92 | 50 | 0 |
| 5* | 81 | 15 | 60 | 0 |
| 6 | 89 | 90 | 78 | 79 |
| 7* | 74 | 75 | 62 | 56 |
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 November 24, 2024.« Back to 2020 American Transplant Congress