Lack of Histological and Molecular Signature Response to Tocilizumab in Kidney Transplants with Chronic Active Antibody Mediated Rejection: A Case Series
Dhiren Kumar, Idris Yakubu, Frough Safavi, Marlon F. Levy, Irfan Moinuddin, Pamela Kimball, Layla Kamal, Anne L. King, Davis Massey, Philip F. Halloran, Gaurav Gupta
Abstract
Background Traditional therapies for caAbMR have unclear efficacy with significant side effects in recipients of kidney transplants (KTs). A recent single-center case series suggested tocilizumab (TCZ) could stabilize renal function and improve microvascular inflammation. Here we report our findings of the use of TCZ in patients with caAbMR. Methods Ten adult recipients of KTs with biopsy-proven caAbMR were treated with TCZ at 8 mg/kg per month. Patients were monitored for adverse events, and therapy was interrupted in the setting of serious infections. Six patients (60%) underwent post-treatment biopsies. Results Patients (mean age of 43 years) were initiated on TCZ at a median of 36 months post-KT. A majority of patients were black (70%), underwent regrafts (40%), and were sensitized (mean cPRA=41%). Patients received a median of six doses of TCZ (range=3–10). At a median follow-up of 12 months (range=8–24 months), renal function did not show improvement (mean eGFR, 42±18 ml/min per 1.73 m 2 to 37±24 ml/min per 1.73 m 2 ; P =0.27). The slope of decline in eGFR remained unchanged (−0.14±0.9 to −0.33±1.1; P =0.25). There was no improvement in mean MVI (g+ptc) (4.8±1.4 to 4.2±2.0; P =0.39) scores or Molecular Microscope Diagnostic System (MMDx) AbMR scores (0.79±0.17 to 0.78±0.26; P =0.86). There was a numeric worsening of chronicity (ci+ct) scores (2.5±0.8 to 3.3±1.7; P =0.38) and MMDx atrophy fibrosis scores (0.36±0.24 to 0.58±0.15; P =0.21). Patient survival was 90%, with one patient death due to complications from a hip infection. Overall death-censored graft survival was 80%, with two graft losses in patients who had recurrent infections requiring hospitalization. Conclusions In this early experience, we report a lack of efficacy and toxicity with the use of TCZ for caAbMR. Prospective clinical trials are needed to clarify the role of IL-6 blockade and the possibility of increased incidence of infections in patients with caAbMR who are treated with TCZ.