Efficacy of Tocilizumab for Refractory Sensitized Patients Awaiting Heart Transplantation

Abstract

<h3>Purpose</h3> Sensitization in patients (pts) awaiting heart transplantation (HTx) can be refractory to conventional therapies such as plasmapheresis, intravenous immunoglobulin (IVIG), rituximab, and bortezomib, particularly for Class II antibodies. Pts refractory to these initial therapies may require more advanced therapies. Tocilizumab is an anti-interleukin-6 monoclonal antibody found to significantly reduce dominant HLA antibodies prior to kidney transplantation. We report here our experience with tocilizumab in refractory sensitized pts awaiting HTx. <h3>Methods</h3> Between 2008 and 2020, we assessed 7 HTx pts who were initially treated with conventional desensitization therapies, including plasmapheresis, IVIG, rituximab, and bortezomib. Pts were then treated with tocilizumab at 8 mg/kg monthly for 6 months. Endpoints included change in calculated panel reactive antibodies (CPRA) determined just prior to the administration of tocilizumab, and 2 weeks after completion of the 6-month therapy. Antibodies were further classified into Class I and Class II to assess efficacy in each of these subgroups. 1 year post-HTx antibody mediated rejection (AMR) and survival was assessed and compared with pts transplanted without desensitization therapy in the same period (N=302). <h3>Results</h3> 6 of 7 sensitized pts treated with tocilizumab had a decrease in their immunodominant antibody with an average 31% reduction. For the CPRA level, 4 of 7 patients had a predominant decrease in Class II circulating antibodies. Post-HTx, compared to pts who did not receive desensitization therapies, 1st year AMR episodes were increased in the tocilizumab group (2.0% vs 14.3% respectively; p=0.032) but this did not affect survival at 1 year (92.1% vs 100% respectively; p=0.447). <h3>Conclusion</h3> Highly sensitized pts on the heart transplant waitlist who are refractory to conventional desensitization therapy appear to be responsive to tocilizumab therapy. Although these pts have more AMR post-transplant, survival is comparable.