New Desensitization Strategy: Daratumumab for Highly Sensitized Pediatric Heart Transplant Candidate

IntroductionAllosensitization represents a barrier to successful heart transplant (HT). It increases waitlist (WL) mortality and may lead to inferior post-transplant outcomes. Strategies to reduce the number of circulating antibodies are utilized with little data on effectiveness of specific desensitization approaches in pediatric HT candidates. We present a case utilizing daratumumab, a monoclonal anti-CD38 antibody, for desensitization in a pediatric patient.Case ReportA 13 month old girl with large intracardiac fibroma was evaluated for HT and found to have significant complement fixing class II HLA antibodies (cPRA 99%) precluding HT. Based on the constellation of heart failure symptoms and expected WL time, decision was made to proceed to VAD support as a bridge to decision and facilitate desensitization. Initial desensitization therapy included plasmapheresis, rituximab, bortezomib, and IVIG, failed to reduce preformed class II HLA antibodies (cPRA remained 99%) and several class II antibodies remained C1q positive. Subsequent desensitization included rituximab, bortezomib and the addition of daratumumab. After receiving 6 doses of daratumumab, the repeat cPRA decreased to 57% with non-complement fixing antibodies present. Unfortunately, the patient experienced a significant GI bleed and required massive blood transfusion leading to rebound antibody development (figure 1). Once the patient was stable, daratumumab therapy was continued and her antibodies levels are presented in figure 1. Throughout desensitization the patient was maintained on IVIG, mycophenolate, and prednisolone. Daratumumab infusions were well tolerated with no major infectious complications. Now with a lower cPRA, she has increased chances for a successful HT.SummaryDesensitization therapy with daratumumab seems to be a safe and promising treatment option for highly sensitized pediatric patients in need for HT.