Carfilzomib for Heart Transplant Desensitization

Abstract

Allosensitization in heart transplant (HT) candidates is associated with longer transplant wait times and post-transplant complications. We summarize our experience with desensitization using carfilzomib (CFZ), an irreversible proteasome inhibitor that causes plasma cell apoptosis. One cycle of desensitization consisted of plasmapheresis and CFZ 20mg/m2 on days 1, 2, 8, 9, 15, and 16 with intravenous immune globulin 2g/kg after CFZ on day 16. Patients underwent repeat cycles as indicated. We summarize treatment impact by depicting calculated PRA (cPRA) for neat combined Class I and II IgG and C1q pre- and post-treatment using a cutoff for cPRA entry of ≥ 4000 and 500 MFI, respectively. We fit a linear mixed model to evaluate treatment effect. From June 2013 to October 2019, 9 patients underwent 20 cycles of CFZ with 6 requiring multiple cycles. Each cycle of CFZ resulted in an average cPRA decrease of 33% (95% CI: 16-50) for combined IgG and 36% (95% CI: 17-55) for C1q. An example is shown in Figure 1. From treatment start to finish, mean cPRA fell from 76% to 35% (p=0.005) for combined IgG and 56% to 4% (p=0.017) for C1q (Table 1). Six of 9 patients have been transplanted with 5 of the transplanted hearts crossing historical antibodies. HT survival at 1 year was 100%. Patient 6 has not been transplanted due to obesity. Patients 3 and 4 only received 4 doses of CFZ due to acute kidney injury, which resolved. Neutropenia, thrombocytopenia, neuropathy, and hepatotoxicity did not occur. CFZ, as part of a desensitization regimen, appears to be safe and effective in sensitized patients awaiting HT. The number of cycles may depend on the HLA antibody titer prior to treatment.