Sutimlimab for treatment of cold agglutinin disease: why, how and for whom?

Therapies for cold agglutinin disease have been directed at the pathogenic B-cell clone. Sutimlimab, a monoclonal antibody that targets C1s, is the first complement inhibitor to be extensively studied in cold agglutinin disease. Sutimlimab selectively blocks the classical activation pathway and leaves the alternative and lectin pathways intact. Trials have documented high response rates with rapid improvement in hemolysis, hemoglobin levels and fatigue scores and low toxicity. Sutimlimab was recently approved in the USA. This drug appears to be particularly useful in severely anemic patients who require a rapid response, in acute exacerbations that do not resolve spontaneously and in patients in whom chemoimmunotherapy is contraindicated or has failed. The choice of therapy in cold agglutinin disease should be individualized.