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A prospective, iterative, adaptive trial of carfilzomib-based desensitization
- Source :
- Am J Transplant
- Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- Oncology
Graft Rejection
Male
medicine.medical_treatment
030230 surgery
chemistry.chemical_compound
0302 clinical medicine
Bone Marrow
HLA Antigens
Isoantibodies
Immunology and Allergy
Pharmacology (medical)
Prospective Studies
Bortezomib
Middle Aged
medicine.anatomical_structure
Treatment Outcome
Toxicity
Female
Oligopeptides
Proteasome Inhibitors
Immunosuppressive Agents
medicine.drug
Adult
medicine.medical_specialty
Adolescent
Plasma Cells
Drug Administration Schedule
Article
03 medical and health sciences
Young Adult
Internal medicine
medicine
Humans
Adverse effect
Aged
Immunosuppression Therapy
Transplantation
Dose-Response Relationship, Drug
business.industry
Carfilzomib
Kidney Transplantation
Regimen
chemistry
Proteasome inhibitor
Plasmapheresis
Bone marrow
business
Biomarkers
Follow-Up Studies
Subjects
Details
- ISSN :
- 16006143
- Volume :
- 20
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
- Accession number :
- edsair.doi.dedup.....6addd2bf9bcc7cbce3859fa78f4742d1