Researchers conducted an open-label extension of the initial phase 1 trial evaluating the safety and efficacy of long-term sutimlimab, a monoclonal antibody targeting the C1s protein of the classical complement pathway, in 4 patients with cold agglutinin disease (CAD) and published their results in the British Journal of Haematology.

The patients were all female, Caucasian, postmenopausal, and aged between 56 and 78 years at the start of the study. Patients received weight-adapted, fixed-dose 1-hour infusions every other week for varying durations, ranging from 13 to 39 months.

For the extension trial, sutimlimab was restarted at a median hemoglobin level of 83 g/L. Treatment with sutimlimab increased hemoglobin to an individual maximum (range) of 126 (117-146) g/L (P =.015). In patients 1 and 2, sutimlimab was able to diminish complement-mediated hemolysis, resulting in peak hemoglobin of 120 g/L. Meanwhile, residual hemolysis was noted in patients 3 and 4, based on undetectable haptoglobin levels.

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Notably, sutimlimab prevented the need for blood transfusions in all patients with CAD. Patient 4 developed a transformation of her previously treated lymphoplasmacytic lymphoma to high-grade lymphoma, and sutimlimab had to be prematurely discontinued.

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There were a total of 130 reported adverse events, 38 of which were classified as grade 1 (mild) events, 88 as grade 2 (moderate) events, and four as grade 3 (severe) events. Overall, 10 adverse events were determined to be related to sutimlimab treatment.

The researchers commented that patients who tested negative for immunoglobulin M (IgM) and immunoglobulin G (IgG) showed a more pronounced response to sutimlimab treatment, whereas hemoglobin levels were lower in patients with positive IgM or IgG. The study’s 3-year follow-up further supports the value of sutimlimab in the treatment of hemolysis in patients with CAD, especially in the context of limitations and side effects associated with current therapeutic options.


Gelbenegger G, Jaeger U, Fillitz M, et al. Sustained sutimlimab response for 3 years in patients with cold agglutinin disease: a phase I, open-label, extension trial. Br J Haematol. Published online June 2, 2022. doi:10.1111/bjh.18289