*Purpose: IL-6 is a cytokine critical for B-cell activation and IgG production. Clazakizumab (CSL Behring LLC) is a humanized monoclonal aimed at the cytokine IL-6. Here we report on 24M follow-up of a single-center Phase I/II study of Clazakizumab for desensitization (DES) in highly-HLA sensitized (HS) patients.

*Methods: Twenty HS patients received PLEX x5 followed by IVIg 2gm/kg X1; then clazakizumab 25mg SC Q4W X6M w. monitoring of HLA antibody. Study end points examined reduction in HLA MFI, rates of transplantation and DSAs pre-& post-tx. Transplanted patients received clazakizumab 25mg Q4W x12M post-tx, induction with alemtuzumab, and maintained on tac/mmf/pred and protocol biopsy @6M.

*Results: 20 HS patients were enrolled. All 20 received DDKT (18 (on-study) and 2 required further DES. Time from dialysis to transplant was 92±54M and from last clazakizumab to transplant was 2.9±4.0M, mean # of clazakizumab doses was 4.4±2.0. All patients had previous transplants; 60% had cPRA>99.95%, 65% were FCMX+/DSA+ @transplant (Table 1). Figure 1A & 1B show the effect of clazakizumab on HLA class I and class II, by strength of MFI pre-DES and 6M post-clazakizumab at neat & 1:8 dilution. Impact on MFIs were: ≥10000: pre- vs. post-DES, class I: 16,742±1137 vs. 10,671±5346 (at neat; p<0.001) and 15,295±1463 vs. 10,709±3802 (1:8 dilution; p=0.005); class II: 17,136±702 vs. 12,879±4282 (at neat; p=0.001) and 15,589±1949 vs. 9337±5136 (1:8 dilution; p<0.001), respectively. AMR episodes occurred in 4 patients with low Banff 2019 scores. Importantly, no DSA rebound was seen in the first-year post-tx. Mean eGFR @24M was 48±38ml/min/1.73m².

*Conclusions: Clazakizumab treatment was associated with significant reductions in HLA alloantibodies and DSAs, increased transplant rates for highly-sensitized patients and low rejection rates. However, confirmation of efficacy for desensitization requires assessment in randomized controlled trials.

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