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Kidney Clinical - Part 1

Sunday March 27, 2022 - 18:00 to 19:10


230.2 Long term tolerability and clinical outcomes associated with Tocilizumab (TCZ) therapy in the treatment of refractory antibody mediated rejection (ABMR) in 25 pediatric renal transplant recipients

Dechu Puliyanda, United States

Pediatric Nephrology
Cedars Sinai Medical Center


Dr. Dechu Puliyanda is a Professor of Pediatrics and the Director of Pediatric Nephrology and Transplant Immunology at the Cedars-Sinai Medical Center in Los Angeles, California. Dr. Puliyanda has over 20 years’ experience with both adult and pediatric kidney transplantation, and her research interests include post-transplant viral infections, biomarkers, and therapeutic strategies for antibody-mediated rejection.


Long term tolerability and clinical outcomes associated with Tocilizumab (TCZ) therapy in the treatment of refractory antibody mediated rejection (ABMR) in 25 pediatric renal transplant recipients

Meghan Pearl2, Patricia Weng2, Aditi Dokras3, Helen Phan Pizzo1, Jonathan Garrison1, Carrie Butler2, Jennifer Zhang2, Elaine F. Reed2, Irene Kim1, Jua Choi1, Mark Haas1, Xiaohai Zhang1, Ashley Vo1, Eileen Chambers4, Robert Ettenger2, Stanley C. Jordan1, Dechu Puliyanda1.

1Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, CA, United States; 2Pediatric Transplant Center, UCLA, Los Angeles, CA, United States; 3Pediatric Transplant Center, UT Southwestern, Dallas, TX, United States; 4Pediatric Transplantation, Duke University School of Medicine, Atlanta, GA, United States

Background: Development of de novo Donor specific antibodies (DSA) post renal transplantation puts pediatric patients at risk for ABMR and allograft failure. 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/Rituximab with or without plasmapheresis and/or Bortezomib. 
Methods: From Jan 2013 to June 2018, we identified 25 patients who had cABMR on biopsy and despite treatment, continued to have cABMR. 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 MFI),  renal function, patient and graft survival and adverse effects of TCZ.  
Results:  Mean age at TCZ: 15.74years (6.3- 21.5yrs) Mean time to ABMR from transplant: 6.3 months (3-154 months). Mean time to TCZ from diagnosis of ABMR: 191days. At diagnosis of cABMR, iDSA was class 2 in 18/25 patients (1 with class 1DSA); and were >10,000MFI in 13/18 patients. 12 (4-26) doses of TCZ was used. TCZ was well tolerated in 22 patients – 2 patients developed fatigue and one patient developed JC viremia and therefore discontinued TCZ infusion.   At median follow up of 36 (10-83) months post ABMR there was no change/decline in the renal function in 24/25patients:  mean delta change in serum creatinine: +0.02mg/dl (1 patient lost allograft). 7/19 patients had resolution of DSA. Side effects : 3 patients had mild transaminitis; 2 had BK viremia, 1 had JC viremia, 1 had thrombocytopenia.  None had CMV viremia. Patient and graft survival was 100%.and 96% respectively.  There was a significant decrease in iDSA  in the 18 patients with HLA DSA at the start of tocilizumab treatment. Follow up biopsies showed reduction in peritubular capillaritis (p=0.015) and C4d scoring (p=0.009). 
Conclusion:  Treatment of ABMR following renal transplantation is challenging. The administration of TCZ in severe ABMR, refractory to B cell immunotherapy, stabilized the progression of ABMR, resulting in preservation of renal function in most patients.  TCZ was fairly well tolerated. The utility of TCZ in the treatment of cABMR should be further explored.