Intro: CAAMR is an increasingly recognized cause of renal allograft failure with limited treatment options. Many patients with CAAMR have engagement of both T and B cell populations, an interaction that partially involves signaling through the IL-6 pathway. Tocilizumab (Toc), an IL-6 receptor blocker is being investigated in sensitized kidney transplant (KT) recipients.

Methods/Results: Since 2014, 10 KT pts were treated with Toc for CAAMR at CUMC. Patients chosen for Toc treatment had persistent CAAMR despite treatment with IV immunoglobulin (IVIG), rituximab, IV steroids and maximal baseline immunosuppression. The majority of pts were female (n=8), first time kidney recipients (n=5) and had DSA at time of AMR on biopsy (n = 9). Eight pts had prior pRBC and/or pregnancy and 3 were crossmatch positive. One pt had delayed graft function and was on hemodialysis (HD) at the time of Toc initiation. Mean age was 35.3±13.3 yrs and the median time to AMR was 151.1 d. Initial AMR were treated with IVIG (n=9), plasmapharesis (n=3) and/or rituximab (n=7). Patients that failed usual treatment were started on Toc at the discretion of the treating doctor. If 4mg/kg was tolerated, dose was escalated to 8mg/kg monthly. Eight pts received concomitant therapy with IVIg 2 gm/kg every other month. Toc was discontinued in one pt due to persistent HD dependence.

The mean Cr was 1.21±0.27 mg/dL at the time AMR was first diagnosed on biopsy, and increased to 2.14±0.56 mg/dL at Toc initiation. Cr improved to 1.95±0.52 mg/d in 6 pts at 3 mo follow-up and 1.85±0.49 mg/dL at 6 mo follow-up. Mean MFI by Luminex of immunodominant DSA (iDSA) in 8 pts did not change significantly following Toc. During a median of 175 d on Toc, proteinuria at AMR diagnosis was 0.307 and decreased to 0.232 at last follow-up. Of 10 pts, 3 had repeat biopsies during follow up. None showed improvement in the cellular rejection component and one pt had decreased C4d intensity. Interstitial fibrosis and glomerular sclerosis were stable on repeat biopsies. There were 3 complications potentially associated with Toc: 2 pts developed BK viremia; 1 had bacterial diarrhea; 1 pt had pharyngeal swelling found to be benign fibrous tissue, unlikely to be associated with immunosuppression.

Conclusion: Following Toc treatment, Cr appeared to stabilize. iDSA remained unchanged and repeat biopsy did not show significant improvement. Toc treatment will have to be studied further before being widely adopted as treatment for persistent CAAMR.

CITATION INFORMATION: Fernandez H, Patel S, Chiles M, Ratner L, Crew R. Tocilizumab as Treatment for Persistent Chronic Active Antibody Mediated Rejection. Am J Transplant. 2016;16 (suppl 3).

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