Impact of carfilzomib-based desensitization on heart transplantation of sensitized candidates

Background: Allosensitization in heart transplant candidates is associated with longer transplant wait times and post-transplant complications. We summarize our experience with desensitization using carfilzomib, an irreversible proteasome inhibitor that causes plasma cell apoptosis.

Methods: One cycle of desensitization consisted of plasmapheresis and carfilzomib 20 mg/m² on days 1, 2, 8, 9, 15, and 16 with intravenous immune globulin 2 g/kg after carfilzomib on day 16. Patients underwent repeat cycles as indicated. We compare calculated panel-reactive antibody (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.

Results: From June 2013 to October 2019, 9 patients underwent 20 cycles of carfilzomib-based desensitization. Each cycle resulted in an average cPRA decrease of 24% (95% CI: 6-42) for IgG and 36% (95% CI: 17-55) for C1q. From treatment start to finish, mean cPRA fell from 76% to 40% (p = 0.01) for IgG and 56% to 4% (p = 0.017) for C1q. Six of 9 patients have been transplanted with 5 of the transplanted hearts crossing preoperative donor-specific antibodies. During a median follow-up of 35.1 months, all transplanted patients have survived with only 1 occurrence of treated rejection. Side effects of desensitization included acute kidney injury (67%) and thrombocytopenia (33%) with all episodes self-resolving.

Conclusions: A carfilzomib-based desensitization strategy among heart transplant candidates reduces the level of HLA antibodies and complement binding, facilitates successful transplantation, and is associated with excellent outcomes at 3 years.