Clazakizumab for desensitization in highly sensitized patients awaiting transplantation

被引:29
作者
Vo, Ashley A. [1 ]
Huang, Edmund [1 ]
Ammerman, Noriko [1 ]
Toyoda, Mieko [2 ]
Ge, Shili [2 ]
Haas, Mark [3 ]
Zhang, Xiaohai [4 ,5 ]
Peng, Alice [1 ]
Najjar, Reiad [1 ]
Williamson, Summer [1 ]
Myers, Catherine [1 ]
Sethi, Supreet [1 ]
Lim, Kathlyn [1 ]
Choi, Jua [1 ]
Gillespie, Matthew [1 ]
Tang, Jacqueline [1 ]
Jordan, Stanley C. [1 ]
机构
[1] Cedars Sinai Med Ctr, Comprehens Transplant Ctr, Los Angeles, CA 90048 USA
[2] Cedars Sinai Med Ctr, Dept Transplant Immunol & Lab, Los Angeles, CA 90048 USA
[3] Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA
[4] Cedars Sinai Med Ctr, Dept HLA, Los Angeles, CA 90048 USA
[5] Cedars Sinai Med Ctr, Immunogenet Lab, Los Angeles, CA 90048 USA
关键词
alloantibody; classification systems; Banff classification; clinical research; practice; desensitization; dialysis; intravenous immunoglobulin; IVIG; kidney transplantation; nephrology; ANTIBODY-MEDIATED REJECTION;
D O I
10.1111/ajt.16926
中图分类号
R61 [外科手术学];
学科分类号
摘要
Alloantibodies are a significant barrier to successful transplantation. While desensitization has emerged, efficacy is limited. Interleukin-6 (IL-6) is an important mediator of inflammation and immune cell activation. Persistent IL-6 production increases the risk for alloantibody production. Here we report our experience with clazakizumab (anti-IL-6) for desensitization of highly HLA-sensitized patients (HS). From March 2018 to September 2020, 20 HS patients were enrolled in an open label pilot study to assess safety and limited efficacy of clazakizumab desensitization. Patients received PLEX, IVIg, and clazakizumab 25 mg monthly X6. If transplanted, graft function, pathology, HLA antibodies and regulatory immune cells were monitored. Transplanted patients received standard immunosuppression and clazakizumab 25 mg monthly posttransplant. Clazakizumab was well tolerated and associated with significant reductions in class I and class II antibodies allowing 18 of 20 patients to receive transplants with no DSA rebound in most. Significant increases in T-reg and B-reg cells were seen posttransplant. Antibody-mediated rejection occurred in three patients. The mean estimated glomerular filtration rate at 12 months was 58 +/- 29 ml/min/1.73 m(2). Clazakizumab was generally safe and associated with significant reductions in HLA alloantibodies and high transplant rates for highly-sensitized patients. However, confirmation of efficacy for desensitization requires assessment in randomized controlled trials.
引用
收藏
页码:1133 / 1144
页数:12
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