Background: Development of de novo Donor specific antibodies (DSA) post renal transplantation puts pediatric patients(pts) at risk for ABMR and allograft failure (Kim JJ AJT 2014). Treatment options for cABMR and Transplant Glomerulopathy (TG) are limited. Interleukin-6 (IL6), secreted by immune cells and macrophages stimulate immune responses, and may be important in mediating cABMR and TG. Here we report our experience with TCZ (anti-IL6R) in pediatric renal transplant recipients with biopsy-proven cABMR, refractory to treatment with IVIg and Rituximab.

Methods: From Jan 2013 to June 2016, we identified 6 pts who developed strong (MFI>10,000) de novo DSAs on annual DSA monitoring, had ABMR on biopsy and despite treatment with IVIg and Rituximab, continued to have cABMR. These patients were treated with TCZ, 4-8mg/kg monthly for 4-12 doses. Pts were monitored for iDSA (immunodominant DSA – DSA with highest MFI)), renal function, patient and graft survival and adverse effects of TCZ.

Results: Mean age at TCZ: 14.2 years (6.3-17.9yrs) Mean time to ABMR from transplant: 2177 days (1159-4036 days). Mean time to TCZ from diagnosis of ABMR: 457 days (185-814 days). At diagnosis of cABMR, iDSA was class 2 in all pts (5 with DQ, 1 with DR) and all iDSAs were >10,000MFI, with C1Q binding. At time of TCZ use, the iDSA were the same since time of diagnosis. 4-12 doses of TCZ was used. TCZ was well tolerated in 4/6 pts – 2 pts developed fatigue and therefore discontinued TCZ infusion after the 4^th dose. At median follow up of 15 months (7-48 months) post TCZ, there was no change/decline in the renal function (mean delta change in serum creatinine: 0.01mg/dl), and no change in the iDSA. WBC counts and liver function tests were stable. 4 pts underwent a renal biopsy 3 months post TCZ, which showed mild to moderate reduction in C4d staining with no worsening of cABMR. Patient and graft survival was 100%. Viral PCRs were negative at and post TCZ.

Conclusion: Development of strong de novo DSA post renal transplantation is associated with cABMR. TCZ was fairly well tolerated in all pts. The administration of TCZ in severe ABMR, refractory to B cell immunotherapy, stabilized the progression of ABMR, resulting in no graft loss and no decline in renal function. iDSA was not affected. The utility of TCZ in the treatment of cABMR should be further explored.

CITATION INFORMATION: Puliyanda D., Kim I., Choi J., Haas M., Zhang X., Vo A., Pizzo H., Jordan S. Safety and Efficacy of Tocilizumab (anti-IL6R, TCZ) Therapy in the Treatment of Chronic Antibody Mediated Rejection (cABMR) in Pediatric Renal Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

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