Impact of carfilzomib-based desensitization on heart transplantation of sensitized candidates

Sriwattanakomen, Roy; Xu, Qingyong; Demehin, Moses; Shullo, M.; Mangiola, Massimo; Hickey, Gavin; Sciortino, Christopher M.; Horn, Edward; Keebler, Mary; Zeevi, Adriana

doi:10.1016/j.healun.2021.03.001

Cited by 21 publications

(16 citation statements)

References 37 publications

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“…Inadequate dosing of CFZ may explain inefficient reduction of bone marrow PC or potentially long-lived plasma cell (LLPC). However, on the basis of the CFZ dose used in desensitization for sensitized patients (27,28), our dosing choice (CFZ, 27 mg/m 2 ) is in keeping with the published literature. However, higher doses of CFZ might be required to achieve better depletion of long-lived PCs.…”

Section: Discussionmentioning

confidence: 95%

Desensitization and belatacept-based maintenance therapy in pregnancy-sensitized monkeys receiving a kidney transplant

et al. 2023

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Among sensitized patients awaiting a transplant, females are disproportionately represented, partly because of pregnancy-induced sensitization. Using female NHPs sensitized by pregnancy alone, we examined the efficacy of costimulation blockade and proteasome inhibition for desensitization. Three animals received no desensitization (control), and seven animals received weekly carfilzomib (27 mg/m 2 ) and belatacept (20 mg/kg) before kidney transplantation. All animals received renal allografts from crossmatch-positive/maximally MHC-mismatched donors. Controls and three desensitized animals received tacrolimus-based immunosuppression. Four desensitized animals received additional belatacept with tacrolimus-based immunosuppression. Multiparous females had less circulating donor-specific antibody when compared to skin-sensitized males before transplantation. While females receiving desensitization showed only a marginal survival benefit over control females (MST = 11 days versus 63 days), additional belatacept to posttransplant maintenance significantly prolonged graft survival (MST > 164 days) and suppressed posttransplant DSA and circulating follicular helper T-like cells. This combination of therapies demonstrates great potential to reduce antibody-mediated rejection in sensitized recipients.

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Section: Discussionmentioning

confidence: 95%

Desensitization and belatacept-based maintenance therapy in pregnancy-sensitized monkeys receiving a kidney transplant

et al. 2023

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“…Sriwattanakomen et al. describe a desensitization regimen with carfilzomib, a second‐generation irreversible proteasome inhibitor, and report a 36% reduction in cPRA over multiple cycles, as well as a reduction in C1q positive antibodies 15 . One of six patients developed AMR.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of bortezomib desensitization among heart transplant candidates

Brinkley

Mangione

Fossey³

et al. 2023

Clinical Transplantation

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Allosensitization is prevalent in heart transplant candidates and is associated with prolonged waiting times and poor outcomes following transplantation. We analyzed the efficacy of a desensitization regimen consisting of plasma exchange, intravenous immunoglobulin, and bortezomib among 25 consecutive sensitized waitlisted candidates at our center from 2016 to 2021. Following desensitization therapies, all C1q negative antibodies were removed from a candidate's unacceptable antigen list. There was a significant decrease in the median number of human leukocyte antigen (HLA) class I (21–15, p = .001) but not class II antibodies (7–6.5, p = .07). There was a significant corresponding decrease in median calculated panel reactive antibodies for class I (90%–74%, p = .004) but not class II (74.5%–75.5%, p = .30). Following desensitization, 76% of patients were transplanted at a median of 91 days. One‐year survival following transplant was 89% with a 33% rate of antibody‐mediated rejection (AMR). In conclusion, a bortezomib desensitization protocol was modestly effective for class I antibodies and allowed successful transplant in most cases when combined with selective crossing of C1q negative antigens.

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“…Carfilzomib (20 mg/m 2 ) was also associated with PP in 9 sensitized patients (PRA >50) waiting for a heart transplant. 79 Six patients received a transplant, and rejection occurred in only 1 patient. Carfilzomib was efficient at significantly reducing IgG and C1q cPRA.…”

Section: Proteasome Inhibitorsmentioning

confidence: 99%

Desensitization in Crossmatch-positive Kidney Transplant Candidates

Noble

Jouve

Malvezzi³

et al. 2022

Transplantation

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Access to kidney transplantation is limited by HLA-specific sensitization. Desensitization strategies enable crossmatch-positive kidney transplantation. In this review, we describe clinical experience gained over the last 20 y using desensitization strategies before kidney transplantation and describe the different tools used (both drugs and apheresis options), including IVIg, rituximab, apheresis techniques, interleukin-6 interference, proteasome inhibition, enzymatic degradation of HLA antibodies, complement inhibition, and B cytokine interference. Although access to transplantation for highly sensitized kidney transplantation candidates has been vastly improved by desensitization strategies, it remains, however, limited by the recurrence of HLA antibodies after transplantation and the occurrence of antibody-mediated rejection.

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Impact of carfilzomib-based desensitization on heart transplantation of sensitized candidates

Cited by 21 publications

References 37 publications

Desensitization and belatacept-based maintenance therapy in pregnancy-sensitized monkeys receiving a kidney transplant

Desensitization and belatacept-based maintenance therapy in pregnancy-sensitized monkeys receiving a kidney transplant

Efficacy of bortezomib desensitization among heart transplant candidates

Desensitization in Crossmatch-positive Kidney Transplant Candidates

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