Session Time: 6:00pm-7:00pm
Presentation Time: 6:20pm-6:25pm
*Purpose: Development of de novo donor specific antibodies (DSA) post renal transplantation puts pediatric patients at risk for chronic Antibody Mediated Rejection (cABMR) and allograft failure. Treatment options for cABMR with transplant glomerulopathy are limited. Interleukin-6 (IL6), secreted by immune cells and macrophages stimulates immune responses, and may be important in mediating cABMR. Here we report our experience with TCZ (anti-IL6R) in pediatric renal transplant recipients with biopsy-proven cABMR, refractory to treatment with IVIg/Rituximab + plasmapheresis +/- Bortezomib.
*Methods: From Jan 2013 to Nov 2018, we identified 25 patients who had ongoing biopsy proven cABMR despite treatment. These patients were treated with TCZ, 4-8mg/kg monthly for a median of 12 (4-26) doses. Patients were monitored for iDSA :immunodominant DSA – DSA with highest Mean Fluorescent Intensity (MFI); renal function, patient and graft survival and adverse effects of TCZ.
*Results: Median age at TCZ: 17.8years (6.3- 21.5yrs). Median time from transplant to cABMR diagnosis: 44 months (3-154 months). Median time to TCZ from diagnosis of cABMR: 191(10-1777) days. At diagnosis of cABMR, 19 patients had iDSA :18 had class II;1 had Class I. 13/18 patients with class II DSA had >10,000 MFI. TCZ was well tolerated in 22/25 patients; 2 patients developed fatigue and one JC viremia and therefore discontinued TCZ. At median follow up of 36 (10-83) months post cABMR diagnosis there was no decline in graft function in 24/25 patients: median delta change in serum creatinine: +0.045mg/dl (-0.80 to 3.42); 1 patient lost allograft. 7/19 patients had resolution of DSA. Side effects of TCZ were: 3 patients had mild transaminitis, 2 BK viremia (no BK nephropathy), 1 JC viremia, 1 thrombocytopenia, 2 leucopenia. None had CMV viremia. 1 patient had previous history of PTLD and one had persistent EBV viremia prior to start of TCZ did not show recurrence of PTLD or worsening viremia. Patient and graft survival were 100% and 96% respectively.
*Conclusions: Treatment of cABMR with transplant glomerulopathy is challenging. Administration of TCZ in cABMR refractory to anti-B cell therapy resulted in preservation of graft function in the majority of patients. TCZ was fairly well tolerated. The utility of TCZ in treatment of cABMR should be further explored.
To cite this abstract in AMA style:Pearl M, Weng P, Dokras A, Pizzo H, Garrison J, Butler C, Zhang JQ, Lim K, Reed E, Kim I, Haas M, Zhang X, Ettenger R, Jordan S, Puliyanda D. Long Term Safety and Efficacy of Tocilizumab (anti-il6r, Tcz) Therapy in the Treatment of Refractory Chronic Antibody Mediated Rejection (cabmr) in 25 Pediatric Renal Transplant Recipients [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/long-term-safety-and-efficacy-of-tocilizumab-anti-il6r-tcz-therapy-in-the-treatment-of-refractory-chronic-antibody-mediated-rejection-cabmr-in-25-pediatric-renal-transplant-recipients/. Accessed July 24, 2021.
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