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For patients awaiting heart transplantation (HTx), who have high levels of circulating antibodies (greater than 70% PRA) desensitization therapy may be indicated. This will allow expansion of the donor pool for a compatible donor. As women appear to be more highly sensitized (due to multiple pregnancies), it is not clear as to whether women compared to men can benefit from desensitization therapy. We sought to answer this question with review of our large, single center database. Between 2008 and 2020, we assessed 49 patients awaiting HTx who underwent desensitization therapy. These patients were divided into groups by sex to evaluate their response to desensitization therapy. Our desensitization protocols consist of regimens including intravenous immune globulin, anti-CD20 monoclonal antibody, plasmapheresis, proteosome inhibitors. A response to desensitization therapy was assessed by the decline of the dominant circulating antibody determined by mean fluorescence intensity (MFI). Post-HTx data was assessed for 1-year survival and freedom from rejections (acute cellular rejection [ACR], antibody-mediated rejection [AMR]). Rejection episodes were compared to a control group of non-sensitized patients transplanted during the same period (n=771). Desensitization therapy in women appeared to be comparable to men considering similar desensitization protocols. There were no significant differences in waitlist mortality, time on the waitlist, or 1-year post-transplant survival, 1-year freedom ACR or AMR, between the two groups. Compared to non-sensitized patients, freedom from AMR was significantly lower in both sensitized men and women (72.7% men and 78.9% women vs. 96.5% control group). Sensitized women awaiting HTx compared to men appear to have similar response to various desensitization regimens. Post-HTx, there was more AMR in both groups, suggesting sensitization may be responsible. [ABSTRACT FROM AUTHOR]

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. 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). 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). 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. [ABSTRACT FROM AUTHOR]