(1148) Successful Use of Carfilzomib and Belatacept to Lower Alloantibodies Prior to Heart Transplant: A Case Series

IntroductionAllosensitized patients have access to fewer compatible donors and face both longer waiting times and higher rates of rejection following heart transplant (HT). Desensitization may provide a pathway for highly sensitized (HS) patients, but is not a universally accepted therapy. We report 2 cases of successful HT following the use of a proteasome inhibitor (carfilzomib, CFZ) with costimulation blockade (belatacept, BTC) to both deplete plasma cells and provide lasting germinal center suppression.Case ReportTwo HS patients were referred to our academic medical center for treatment with this novel desensitization protocol. A treatment cycle consisted of 6 twice-weekly doses of CFZ, and BTC 10 mg/kg on days 1, 5, 9, 15, and 29 followed by 5 mg/kg every 28 days. Patient A is a 20-year-old woman who required re-transplant due to coronary allograft vasculopathy. She completed 2 cycles of CFZ-BTC complicated by some worsening neuropathy. Calculated PRA (using C1q complement-fixing antibody testing) was Class I 1%, Class II 99% after 2 cycles; these antibodies were listed as unacceptable and the patient was transplanted following a negative prospective complement-dependent-cytotoxicity crossmatch 20 days after listing. She experienced an episode of 2R rejection at 9 months that was treated with a steroid pulse. Patient B is a 33-year-old woman with congenital heart disease palliated with a homograft. She experienced hypotension but was able to complete one cycle of CFZ-BTC. Calculated PRA dropped to Class I 9% and Class II 0% after which she was successfully transplanted. She has not had any rejection. Graft and patient survival are both currently 100% at 9- and 6-months post-transplant.SummaryDesensitization with CFZ-BTC appears efficacious and well-tolerated. Excellent graft and patient survival without significant episodes of rejection suggests that CFZ-BTC may provide a viable path to transplant for other HS transplant candidates.