INTRODUCTION: ~30% of HS patients fail to respond to DES with IVIG+rituximab. IL6/IL-6R signaling is critical for B-cell differentiation to plasmablasts and IgG production. Tocilizumab (TCZ) is a 1^st in-class monoclonal directed at the IL-6R. TCZ treatment in humans inhibits T_FH & Th₁₇ cells while increasing T_regs and suppressing plasmablasts. We previously reported on the efficacy of TCZ as a DES agent. Here we report our extended experience using DES with PLEX+IVIG+TCZ. PATIENTS & METHODS: From 12/7/10 – 6/29/16, 26 HS patients were DES with PLEX+IVIG+TCZ. Acceptable crossmatch criteria included: negative CDC-CMX, FCMX ≤225MCS and DSA ≤10,000MFI post-DES. Unacceptable antigens were defined as MFI>15000. Transplanted patients received induction with alemtuzumab and maintained with tac/mmf/pred + monthly TCZ x6M. Patient & graft survival, eGFR, freedom from ABMR and change in DSA levels post-TCZ were analyzed. RESULTS: Ten patients did not achieve DSA reduction sufficient for transplantation after TCZ. All had previous transplants and multiple C1Q+ HLA specificities with CPRA 99-100% {G1}. However, 16 patients were transplanted after TCZ DES {G2}. Briefly, 11 patients were FCMX+/DSA+ @transplant. Three patients developed ABMR post-transplant, but responded to PLEX/IVIG/Ritux and continuation of TCZ X 6M (Figure 1). A significant reduction in DSA from pre- to post-transplant was seen in TCZ treated patients (P<0.03) (Figure 2). Patient & graft survival up to 36M was 100%. Mean time to transplant from 1^st DES was 28±17.5M. However, after TCZ,was 4±3.3M. Finally, eGFR were similar at 12M, 24M & 36M (~57±21 ml/min/1.73m²). CONCLUSIONS: 26 patients were DES with TCZ. Sixteen patients received incompatible transplants with no patient or graft loss. Three patients developed ABMR, usually after cessation of TCZ therapy. TCZ DES resulted in significant reduction of DSA post-transplant. Therefore, TCZ may offer benefit in improving rates of transplant for HS patients who fail to respond to IVIG+rituximab therapy and benefits in maintaining the allograft long-term. [figure2]

CITATION INFORMATION: Vo A, Choi J, Kim I, Huang E, Louie S, Kang A, Williamson S, Myers K, Peng A, Najjar R, Jordan S. Extended Experience with Tocilizumab (Anti-IL6R) for Difficult to Desensitize (Des) Patients Awaiting HLA Incompatible Kidney Transplant. Am J Transplant. 2017;17 (suppl 3).

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