CD38-targeted therapy with Daratumumab in clinical lung transplantation: A single-center experience.

Background: Antibody-mediated rejection remains a major threat to long-term graft function after lung transplantation. Current therapies aim to eliminate circulating antibodies and suppress B-cell-activity but often fail to reduce donor-specific antibodies. Daratumumab, a monoclonal antibody targeting CD38, has shown potential in depleting antibody-producing plasma cells. This study investigates the clinical application of daratumumab in lung transplant recipients. Methods: We performed a retrospective single-center study including all lung transplant recipients treated with subcutaneous daratumumab for antibody-mediated rejection A total of 14 patients with newly developed donor-specific antibodies and clinical antibody-mediated rejection were analyzed. Results: In all patients with AMR, antibodies directed against human leukocyte antigen class I decreased to less than 25-50% of baseline levels within 12 weeks. Antibodies against class II also declined in 5 patients. Eleven patients survived the initial AMR episode. Chronic lung allograft dysfunction was already present in several patients before the AMR episode, while others developed CLAD during follow-up. The treatment was generally well tolerated with the most common side effects being leukopenia, hypogammaglobulinemia and infections. Conclusions: CD38-targeted therapy with daratumumab may represent a promising addition to the antibody mediated rejection treatment panel.