The Novel Use of Daratumumab in the Treatment of Refractory Autoimmune Pulmonary Alveolar Proteinosis

Autoimmune pulmonary alveolar proteinosis (aPAP) is caused by circulating anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies that impair alveolar macrophage and neutrophil function. Macrophage dysfunction leads to accumulation of protein- and lipid-rich surfactant within alveoli, impairing gas exchange and leading to respiratory failure. Standard treatments include whole lung lavage (WLL) as first-line therapy, nebulised replacement of GM-CSF, and in refractory cases, lymphocyte depletion, immunosuppression, or lung transplantation. We present a case of a 51-year-old patient with severe, treatment-refractory aPAP failing all standard PAP therapies. A compassionate access program enabled commencement of Daratumumab, a CD38-directed monoclonal antibody (mAb), targeting long-lived plasma cells and providing a novel approach to treatment-resistant autoimmune conditions. One year post completion of Daratumumab, the patient remained in remission with clinical and radiological improvement. There was a corresponding reduction in anti-GM-CSF antibody levels and improvement in gas exchange on pulmonary function testing.