C007 | EFFICACY AND SAFETY OF SUTIMLIMAB IN COLD AGGLUTININ DISEASE IN THE REAL WORLD

Cold agglutinin disease (CAD) is an immune mediated hemolytic anemia characterized by complement mediated hemolysis. Sutimlimab has shown high efficacy in increasing Hb levels and reducing hemolytic markers in two phase 3 trials. Data on the real world use of sutimlimab are lacking. We retrospectively collected clinical and hematological parameters of CAD patients treated with sutimlimab in the post-trial access/compassionate use program in Italy, France, and UK. Twenty-five CAD patients (15 females, median age 65 years, range 50-82) were included; Direct antiglobulin test was positive for C3d in 20 and for IgG+C+ in 5 patients; median cold agglutinin titer was 256 (range 4-2048), and 21 patients had the typical B-cell infiltrate at bone marrow aspirate. Patients had received a median of 3 therapy lines (1-4) before sutimlimab, including steroids (N=20), rituximab (23), and rituximab-bendamustine (6). Complications pre-sutimlimab included 7 infections (> G3) and 6 thromboses. The median number of transfusion in the last 6 months pre-sutimlimab was 3 (0-18). At baseline median Hb levels were 8.9 g/dL (2.9-10.8), LDH 1.6 xULN (0.8-3.6), unconjugated bilirubin 2.1(0.8-2.8), reticulocytes 131x10^9/L(10-340). Sutimlimab was given at 7.5 g iv/14 days after loading in 6 patients, and at 6.5 g in 19, either as single-agent in 16 or along with erythropoietin in 8 and prednisone in 1. Median treatment follow-up was 17 months (6-81). Figure 1A shows Hb increase in the first 2 weeks (median +2 g/dL, +2.85 g/dL at 4 weeks,+2.95 g/dL), followed by stable levels until the 24 months follow up. Corresponding response rates (PR+CR) were 76%, 87%, 83%,77%, 80%, 70%, 69%, 72%, and 88% at the various timepoints (Figure 1B). Further 12% of cases had Hb increase and all but one patient resolved transfusion dependence. Three patients stopped sutimlimab because of no response and persistent transfusion need, overt Waldenstrom macroglobulinemia (WM), and patient decision. Eight patients had infection (G3 in 7), 1 thrombosis (DVT of basilic vein), and 4 hemolytic exacerbations. At the last follow up only one patient had died due to progressive WM with sepsis. In conclusion, sutimlimab confirmed to be an effective treatment in improving anemia and resolving transfusion dependence in more than 70% patients in the real world.