Dr. Yougandhar Akula (YA), from the University of Mississippi in Jackson, Mississippi, discusses his abstract for the National Kidney Foundation’s 2016 Spring Clinical Meetings (SCM16), Eculizumab with Bortezomib Based Immunosuppression for Renal Allograft Rejection: A Case Series, with Dr. Kenar Jhaveri, AJKD Blog Editor.
AJKDblog: Why don’t you tell us a little about your research and abstract being presented at the NKF 2016 Spring Meetings?
YA: We present a case series in which patients with acute antibody mediated rejection (AMR) were managed with both eculizumab and bortezomib. Allograft survival after kidney transplantation can be reduced with the development of donor-specific antibodies. Conventional therapies of acute antibody mediated rejection and desensitization regimens were based on antibody neutralization (IVIG), antibody removal (plasmapheresis), and B-cell targeting (rituximab, alemtuzumab). More recently, the role of bortezomib (a proteasome inhibitor that causes plasma cell apoptosis/depletion) in AMR has been described. Eculizumab is a humanized mAb against complement protein C5, and currently, clinical trials are underway to assess its use in AMR. Although bortezomib and eculizumab were separately used to manage AMR, we report the use of both drugs to manage AMR. The three patients described in the case series were treated with single dose of eculizumab along with rituximab, solumedrol, bortezomib, and IVIG. Two of the three patients received plasmapheresis. All the patients recovered renal function without major complications.
AJKDblog: Based on your experience, can you summarize the patient profile who should receive this agent for rejection?
YA: Eculizumab should be considered when managing patients with rapid loss of graft function, high titer of donor-specific antibodies, and renal transplant biopsy showing high grade cortical necrosis. The cost of the drug is a limiting factor that prevents its wide spread use in the treatment of AMR. Some patients with AMR lose graft function despite management with treatment protocols involving either bortezomib or eculizumab. This suggests a complex interplay of antibodies, cell-mediated immunity, and complement pathways in AMR. Clinical trials are needed to determine the role and duration of combination treatment (bortezomib, eculizumab) in the management of AMR.
AJKDblog: Where do you and your group go from here?
YA: Patients treated with the above protocol continued to be monitored for long-term safety of the regimen. So far, all three patients have good allograft function. We continue to use eculizumab in selected patients to manage AMR.
All Spring Clinical Meeting abstracts are available in the May issue of AJKD.