Treatment of Cold Agglutinin Syndrome Secondary to Chronic Lymphocytic Leukemia With Sutimlimab and Obinutuzumab-Venetoclax.

Abstract

Cold agglutinin-mediated autoimmune hemolytic anemia (AIHA) is a rare disorder in which IgM autoantibodies lead to complement-dependent hemolysis and cold-induced circulatory symptoms. It is categorized as either cold agglutinin disease (CAD), a primary lymphoproliferative disorder (LPD), or cold agglutinin syndrome (CAS), which occurs secondary to other conditions most commonly infections or lymphoid malignancies. Although the treatment for CAS should be directed toward the underlying condition, the often slower response rates of these treatments, especially in the setting of LPD, could necessitate other strategies for patients with severe hemolytic anemia requiring more rapid control of hemolysis. For patients with CAD, inhibition of the classical complement pathway with the C1s inhibitor sutimlimab has demonstrated significant control of hemolysis, resolution of anemia, and improvement in quality of life. However, little has been published regarding the use of sutimlimab for the treatment of CAS. Here, we describe a patient with CAS secondary to chronic lymphocytic leukemia (CLL) with severe IgM-driven complement-mediated hemolysis who was successfully treated with a combination of sutimlimab and CLL-directed therapy with obinutuzumab-venetoclax. Sutimlimab provided rapid cessation of hemolysis, acting as a bridge while the obinutuzumab-venetoclax addressed the underlying CLL that was presumably responsible for the autoantibody production. This case demonstrates that combining sutimlimab with obinutuzumab-venetoclax is an effective and safe treatment for patients with CAS in the setting of CLL, supporting the use of short-term sutimlimab for CAS as a bridge to more durable treatment for underlying LPD such as CLL.