Use of Daratumumab for Desensitization Prior to Cardiac Transplantation: A Case Report

Introduction Heart transplant candidates with allosensitization face higher waitlist mortality and may have inferior post-transplant outcomes. We present our experience with a multi-drug desensitization regimen including daratumumab, an anti-CD38 monoclonal antibody, in a 51-year-old female listed for heart transplant. Case Report The patient presented with heart failure due to NICMP with LMNA mutation. She was listed for heart transplant with 94% class I PRAs and 98% class II PRAs. Given level of sensitization, the decision was made to desensitize with plasmapheresis (5 sessions), IVIG (2 g/kg), bortezomib (4 doses), and tocilizumab (1 dose). During this treatment she experienced neutropenia requiring bortezomib dose reduction. Following these therapies her class I PRA decreased to 36%, but her class II PRA persisted at 99%. Immunodominant HLA antibodies are trended in Figure 1. She subsequently received additional plasmapheresis (6 sessions) with IVIG (2 g/kg) and rituximab (1 dose). PRAs remained consistent; HLA MFIs remained high (Figure 1). She was then treated with daratumumab weekly. She received 8 doses; the last dose was received the day prior to transplant. Her class I PRA decreased to 13% and class II PRA was 99% at the time of transplant. Her crossmatch was negative, and she received steroid induction alone. Maintenance immunosuppression consisted of tacrolimus, mycophenolate, and prednisone. Her tacrolimus was therapeutic by POD6 with a goal of 10-15 mcg/mL. By month 11 post-transplant she has had no episodes of cellular or antibody-mediated rejection. Graft function has been stable with ejection fraction >60%. All DSA screening has been negative and she has not developed any significant infections post-transplant. Summary Daratumumab, as part of a desensitization regimen, appears to be safe and effective in sensitized patients awaiting heart transplant and was not associated with post-op complications, and may have contributed to prevention of antibody-mediated rejection post-transplant.