NEW IMMUNOSUPPRESSIVE AGENTS

M.J. Everly¹, P.I. Terasaki^2
1, One Lambda Inc, Canoga Park/UNITED STATES OF AMERICA, ², Terasaki Foundation Laboratory, Los Angeles/UNITED STATES OF AMERICA

Body: Introduction: In 2008, proteasome inhibitors were introduced as a new option for treatment of antibodies and antibody mediated injury in the transplantedpatient. Since that time many centers started using bortezomib in transplant recipients and candidates. Herein, we summarize the new evidence of bortezomib use across 29 centers worldwide.

Methods: A request for case reports on bortezomib use in transplant was made in January 2010. 69 case reports from 29 centers were submitted as part of this request. In this analysis, 69patients were included. Outcomes measure were antibody response for all cases (defined as a 50% reduction in all DSA), allograft stabilization for rejection episodes, and successful transplantationfor desensitization patients.

Results: Of the 69 patients, 12 were desensitization, 18 for initial acute antibody mediated rejection (AAMR) treatment, 27 for refractory AAMR, and 12 for chronic AMR. In the 45 cases of AAMRcombined, 44 patients had improvement or stabilization of allograft function (Figure 1). Regarding antibody response, 19 of the 39 (6 unreported) showed a HLA antibody reduction. In chronic rejectionand desensitization the results were also promising, but to a lesser degree. Half of desensitization cases were transplanted, and 42% of chronic rejection cases stabilized. In all cases, the moderaterate of HLA reduction is thought to be due to bortezomib-alone regimens, excluding these cases increase HLA reduction success, indicating combination therapy may be needed. Finally, regardingtoxicity, all side effects were transient, but a few rare side effects were reported (EBV hepatitis, BK viremia, bacterial pneumonia, and AV block).

Conclusion: This report of 69 cases constitutes the first use of bortezomib in many of the 29 centers. Despite lack of experience with the drug, results are promising, leading to stabilizationin the majority of rejections and desensitizing 50% of the highly sensitized cases. Among regimens used, bortezomib alone was shown to permit clinical improvement but has only moderate efficacy onantibody reduction, indicating the need for combination regimens with therapies such as plasmapheresis. In all, this data constitutes a start in a new direction to improving allograft outcomes.

Disclosure: All authors have declared no conflicts of interest.