Sutimlimab is a monoclonal antibody against complement fraction C1s approved for the treatment of hemolytic anemia due to cold agglutinin disease (CAD). Here, we analyzed and report the largest international CAD cohort of sutimlimab-treated patients ever reported to highlight its safety and effectiveness in the real-world setting. We accrued a cohort of 57 CAD patients (median age 73.5 years, 56% females). At baseline, patients had severe to moderate anemia (median Hb 8.9 g/dL) and active hemolysis, with a substantial transfusion burden despite a median of 2 prior therapies, including corticosteroids and rituximab. After sutimlimab initiation, median Hb increased by 2 g/dL within 2 weeks and reached 12 g/dL in 4 weeks, remaining stable up to 24 months. This improvement was paralleled by an early and durable normalization of hemolytic markers. Objective responses were observed in most patients by week 2, with complete responses in approximately 50% by Week 4 and 55%-60% during long-term follow-up. Peripheral cold-induced symptoms did not improve and were associated with reduced response rates. Inadequate reticulocytosis also predicted poorer response and suggests the combination with recombinant erythropoietin. Sutimlimab was generally well tolerated. Infections were the most frequent adverse events (23%); severe infections predominantly occurred in previously rituximab-treated individuals. Hemolytic exacerbations occurred in 16% of cases, mostly due to infections. Thrombotic complications were rare. Overall, sutimlimab demonstrated rapid, durable effectiveness and a favorable safety profile in heavily pretreated real-world CAD patients.
Keywords: cold agglutinin disease; complement; infections; rituximab; sutimlimab.
© 2026 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.