First Report of Daratumumab in Clinical Lung Transplantation

Abstract

<h3>Purpose</h3> Antibody mediated rejection (AMR) after lung transplantation is difficult to treat and often results in death or graft loss. Therapies targeting antibodies or B cells are in many cases inadequate for decreasing donor specific antibodies (DSA), particularly when they are directed against MHC class II. Daratumumab (DAR) is a humanized anti-CD38 monoclonal antibody, which induces plasma cell death through multiple mechanisms including complement- dependent cytotoxicity, antibody-dependent phagocytosis, and apoptosis. Based on these properties it may have the potential to reduce the amount of DSAs and therefore improve outcome after AMR. <h3>Methods</h3> Retrospective analysis of all patients who received daratumumab as an add on rescue therapy for AMR or for desensitization pre/post-transplant at our center. <h3>Results</h3> Six patients received daratumumab due to the following reasons: 5 patients with de novo DSAs and AMR, 1 patient with pre-transplant DSAs and post-transplant immunadsorption without clinical AMR. Daratumumab was safely administered with just mild infusion reactions and no severe adverse event. Of not, none of the patients developed and infectious complication. Five of the 6 patients showed a significant decrease of their DSAs with a reduction of MFI values after 6-8 weeks to <50% of the baseline . Despite this early success, four patients developed CLAD (,two of which required retransplantation. The remaining two patients stabilized with their lung function and did not develop CLAD. <h3>Conclusion</h3> Treatment for AMR remains challenging, especially in the presence of class II HLA antibodies. Daratumumab might be a promising addition to the AMR treatment panel, prospective clinical studies are needed.