Daratumumab monotherapy as a desensitization strategy prior to cardiac transplantation.

BACKGROUND Human leukocyte antigen (HLA) sensitization is a significant barrier to transplantation for many patients. Daratumumab has proven safety and tolerability in multiple myeloma. We hypothesized that daratumumab monotherapy could be an effective and safe desensitization strategy in highly sensitized patients awaiting cardiac transplantation. OBJECTIVES The primary end-point of this trial was the scope of daratumumab in lowering HLA antibodies. Secondary end-points included presence of donor-specific antibody, incidence of cellular and antibody-mediated rejection (AMR) and cardiac allograft function. METHODS Six consecutive highly sensitized patients were enrolled who had a calculated panel reactive antibody >50% using a mean fluorescence intensity (MFI) threshold >4,000 through a single antigen bead assay. Three completed the full 8 weeks of daratumumab therapy. HLA antibodies with MFI >10,000 were considered unacceptable for donor offers. All patients received weekly doses of 1,800 mg daratumumab and 30,000 units hyaluronidase subcutaneously for a planned total of 8 weeks. RESULTS There was a significant reduction in HLA class I and class II antibodies by the time of heart transplantation. Daratumumab was well tolerated and without any serious adverse events. By the time of this publication, 5 of the total of 6 patients enrolled have been successfully transplanted. None of the patients enrolled experienced AMR and maintain normal cardiac allograft function. CONCLUSIONS Daratumumab monotherapy may be a safe and effective desensitization strategy in highly sensitized patients who are otherwise eligible for heart transplantation and considered too ill for other desensitization strategies.