*Purpose: IL-6 is a critical cytokine for plasma cell IgG production. Clazakizumab (CSL Behring LLC) is a humanized monoclonal aimed at the cytokine IL-6. Here we report on 12M follow-up of Phase I/II study of Clazakizumab for DES in highly-HLA sensitized (HS) patients.

*Methods: Twenty HS patients received PLEX x5 followed by IVIg 2gm/kg X1; then claza, 25mg SC Q4W X6, with monitoring of HLA antibody and immune parameters. Study end points examined reduction in HLA MFI, rates of transplantation and DSAs pre-& post-tx. Transplanted patients received claza 25mg SC Q4W for up to 12M post-tx, induction with alemtuzumab, and maintained on tac/mmf/pred and protocol biopsy @6M.

*Results: Eighteen of 20 showed reduction of HLA MFI after desensitization; 16 were transplanted. Time from dialysis to transplant was 102±54M and from last claza to transplant was 2.5±3.5M. All patients had previous transplants; 63% had cPRA 99-100%, 50% were FCMX+ and 75% were DSA+ @transplant. Figure 1A shows % reduction in MFI specificities after desensitization for CI+II of individual patient. Figure 1B shows that claza Des resulted in a mean reduction of MFI of 45±33% for CI+II HLA antibodies. Figure 2 shows reduction of DSA MFI pre ->12M post-tx. One patient had detectable DSA out to 12M post-tx. Three patients developed rejection CMR/cABMR episodes. Mean eGFR @12M was 56±30ml/min.

*Conclusions: Claza treatment resulted in a significant reduction in MFI for CI&II specificities. Only 1 patient had detectable DSAs after 12M post-tx. Clazakizumab appears promising as a desensitization agent when used with PLEX+IVIg.

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