Researchers reviewed the current therapies for cold agglutinin disease (CAD) and determined that reducing monoclonal immunoglobulin M (IgM) synthesis constitutes rituximab, bortezomib, and bendamustine, as published in Hematology/Oncology Clinics of North America. In contrast, new approaches focus on impeding complement activation with sutimlimab while reducing the use of cytotoxic agents.

The literature review conducted by Morie A. Gertz, MD, MACP, included 35 publications from 2012 to 2021 and highlighted important updates about CAD. Regarding the diagnosis, Dr. Gertz recommends that all patients with a positive Coombs test undergo further testing for complement-mediated hemolysis since noticing that such diseases are rarely present with a negative Coombs test. Furthermore, a bone marrow biopsy remains an essential diagnostic tool.

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As for treatment, Dr. Gertz noted the evolution of the recommended drugs. “Historically, treatment has been directed toward the elimination of the lymphoplasmacytic cells responsible for the synthesis of the IgM protein,” she said.

“The standard therapies for warm hemolytic anemia including corticosteroids, splenectomy, and intravenous immunoglobulin infusions are typically ineffective . . . There use is, therefore, discouraged in CAD.”

Nowadays, sutimlimab, a humanized monoclonal antibody, constitutes a key therapeutic option for CAD. With a response rate of 85%, only surpassed by ibrutinib, this drug also has a low risk of side effects. Even though almost all users admitted to experiencing adverse reactions, less than 40% could be attributed to sutimlimab, and most were considered mild. 

“Primary therapy is directed at the suppression of the cells in the bone marrow responsible for the production of the IgM monoclonal protein,” Dr. Gertz concluded. “Promising studies with the use of complement inhibition as a strategy to interrupt hemolysis are forthcoming.”


Gertz M. Updates on the diagnosis and management of cold autoimmune hemolytic anemia. Hematol Oncol Clin North Am. Published online March 10, 2022. doi:10.1016/j.hoc.2021.11.001