A prospective, iterative, adaptive trial of carfilzomib-based desensitization.

Autor: Tremblay S; Division of Transplantation, Department of Surgery, University of Cincinnati, Cincinnati, Ohio., Driscoll JJ; Division of Transplantation, Department of Surgery, University of Cincinnati, Cincinnati, Ohio.; University of Cincinnati Cancer Institute, Cincinnati, Ohio., Rike-Shields A; Division of Transplantation, Department of Surgery, University of Cincinnati, Cincinnati, Ohio.; The Christ Hospital, Cincinnati, Ohio., Hildeman DA; Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio., Alloway RR; Division of Nephrology, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio., Girnita AL; Division of Transplantation, Department of Surgery, University of Cincinnati, Cincinnati, Ohio.; Transplantation Immunology Division, Hoxworth Blood Center, Cincinnati, Ohio., Brailey PA; Transplantation Immunology Division, Hoxworth Blood Center, Cincinnati, Ohio., Woodle ES; Division of Transplantation, Department of Surgery, University of Cincinnati, Cincinnati, Ohio.
Jazyk: angličtina
Zdroj: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2020 Feb; Vol. 20 (2), pp. 411-421. Date of Electronic Publication: 2019 Oct 23.
DOI: 10.1111/ajt.15613
Abstrakt: Proteasome inhibitor-based strategies hold promise in transplant but have yielded varying results. Carfilzomib, a second-generation proteasome inhibitor, may possess advantages over bortezomib, the first-generation proteasome inhibitors. The purpose of this study was to evaluate the safety, toxicity, and preliminary efficacy of carfilzomib in highly HLA-sensitized kidney transplant candidates. Renal transplant candidates received escalating doses of carfilzomib followed by plasmapheresis (group A) or an identical regimen with additional plasmapheresis once weekly before carfilzomib dosing. Thirteen participants received carfilzomib, which was well tolerated with most adverse events classified as low grade. The safety profile was similar to bortezomib desensitization; however, neurotoxicity was not observed with carfilzomib. Toxicity resulted in permanent dose reduction in 1 participant but caused no withdrawals or deaths. HLA antibodies were substantially reduced with carfilzomib alone, and median maximal immunodominant antibody reduction was 72.8% (69.8% for group A, P = .031, 80.1% for group B, P = .938). After depletion, rebound occurred rapidly and antibody levels returned to baseline between days 81 and 141. Bone marrow studies revealed that approximately 69.2% of plasma cells were depleted after carfilzomib monotherapy. Carfilzomib monotherapy-based desensitization provides an acceptable safety and toxicity profile while leading to significant bone marrow plasma cell depletion and anti-HLA antibody reduction.
(© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze: MEDLINE
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