Sutimlimab in Patients With Cold Agglutinin Disease ( <scp>CAD</scp> ): Results From a Managed Access Program

Cold agglutinin disease (CAD) is a low-grade lymphoproliferative disorder accounting for 15%-30% of patients suffering from autoimmune hemolytic anemias. The clonal B cells produce autoantibodies primarily of the IgM-κ class that cause agglutination of red blood cells (RBCs) at temperatures ≤ 37°C and activate the classical complement pathway with subsequent RBC destruction. Before the approval of the monoclonal antibody sutimlimab, treatment options were limited. Sutimlimab inhibits the classical complement pathway at C1s while sparing the lectin and alternative complement pathways. Efficacy, safety and tolerability of sutimlimab have been established in the multicenter CARDINAL and CADENZA trials. In the present investigation, 10 patients on sutimlimab were followed up to 96 weeks in the Managed Access Program (MAP) in Essen. Eight of these patients had previously participated in the multicenter trials and were restarted on sutimlimab after a median washout period of 12.6 weeks. In addition, two sutimlimab-naive patients were included. Hemoglobin concentration increased in all patients (median hemoglobin concentration before therapy 9.8 vs. 12.5 g/dL at the end of the study). Bilirubin levels normalized already after 2 weeks in all patients. Reticulocyte count declined in nine, haptoglobin and hemopexin concentrations normalized in six and 10 patients, respectively. In conclusion, the present investigation with primary CAD patients in a single center demonstrates long-term normalization of laboratory parameters, abrogation of specific clinical symptoms and absence of drug-related side effects with sutimlimab.