Monoclonal antibodies for treatment of cold agglutinin disease.

Conventional treatment of CAD includes a B cell targeted treatment approach with rituximab, yielding only limited treatment success. Addition of a cytotoxic agent (e.g. bendamustine) increases efficacy but this is accompanied by an increased risk of neutropenia and infection. Novel complement-directed therapies have emerged and were shown to have a good efficacy against hemolysis and safety profile but are expensive and unable to address circulatory symptoms. Complement inhibition with sutimlimab may be used as a bridging strategy until B cell directed therapy with rituximab takes effect or continued indefinitely if needed. Future antibody-based treatment approaches for CAD involve the further development of complement-directed antibodies, combination of rituximab and bortezomib, and daratumumab. Non-antibody based prospective treatments may include the use of Bruton tyrosine kinase inhibitors.