First Interim Analysis of Patients with Cold Agglutinin Disease (CAD) Patients and the Sutimlimab-Treated Subgroup from the Cadence Registry
Authors: Broome Catherine M. , Michel Marc , Barcellini Wilma , Jaeger Ulrich , Ueda Yasutaka , Hill Quentin A. , Cid Joan , Wu Jiangming , Srivastava Shruti , Wardęcki Marek , Patel Reena , Yoo Ronnie , Röth Alexander 
Published: December 2024

Introduction
The CADENCE Registry (NCT05791708) is a large international database of patients (pts) with cold agglutinin disease (CAD) or cold agglutinin syndrome (CAS, a cold antibody-driven hemolytic anemia associated with an underlying condition). CADENCE is aimed at understanding the patient demographics, clinical characteristics, treatment patterns, healthcare resource utilization, natural history of disease, long-term clinical outcomes, and impact on patient quality of life. Sutimlimab (SUT) is a humanized monoclonal antibody that selectively inhibits the classical complement pathway by inactivating C1s and is the first approved treatment for CAD. CADENCE includes a SUT cohort with an objective to assess the safety and the effectiveness of SUT in pts with CAD in a real-world setting. Here we report the data from the first interim analysis on the CAD subgroups based on treatment status.
Methods
Adults ≥18 years of age, diagnosed with CAD or CAS were included. Of 140 pts enrolled at time of analysis (data cutoff: October 6, 2023) 133 pts (7 pts excluded: eligibility criteria unmet) were included in the analysis (CAD, n=112; CAS, n=21).
Results
The treatment status among CAD pts (based on investigator-reported medications used to treat CAD) at enrollment was treatment-naive (n=50), CAD-SUT ongoing (n=15), other CAD treatment ongoing (n=33), previously on CAD therapy (n=14). The mean (SD) age of pts in the total CAD group and CAD-SUT subgroup at enrollment was 72.0 (10.29) and 74.1 (8.14) years, respectively. The mean (SD) time (months) from diagnosis to first treatment was 32.08 (48.49) in the CAD group and 55.59 (58.26) in the CAD-SUT subgroup. At diagnosis, mean (SD) hemoglobin (Hb) levels were 9.61 (2.22) g/dL and 9.40 (1.88) g/dL, mean (SD) bilirubin levels were 1.95 (0.83) mg/dL and 1.65 (0.37) mg/dL in the CAD group and CAD-SUT subgroup, respectively.
At enrollment, Hb was well controlled with mean (SD) levels of 11.25 (1.86) g/dL in the total CAD group and 11.55 (2.02) g/dL in the CAD-SUT subgroup. At enrollment, hemolysis was better controlled in the CAD-SUT subgroup as indicated by the normalization of mean (SD) bilirubin levels (mg/dL) [1.15 (0.94) mg/dL]; compared to 1.64 (0.98) mg/dL in the CAD group. Demographics and clinical characteristics similar to the CAD group were observed in pts with CAS.
At enrollment, the FACIT-Fatigue [CAD, 34.93 (12.77); CAD-SUT, 41.83 (11.06)], SF-36 PCS [CAD, 42.89 (10.50); CAD-SUT, 47.86 (8.15)], and SF-36 MCS [ CAD, 48.03 (11.07); CAD-SUT, 50.46 (12.64)] scores were higher in the CAD-SUT subgroup, compared to the CAD group. At enrollment, the proportion of physicians assessing patient response to current treatment as “excellent” or “good” was higher in the CAD-SUT subgroup (91.7%) than the total CAD group (68.5%).
Prior to or at enrollment, 55 (49.1%) and 7 (33.3%) pts received any transfusion in the total CAD and total CAS group. The number of pts that received any transfusion in subgroups were: 14 (28.0%) treatment-naive, 9(60.0%) CAD-SUT ongoing, 26 (78.8%) other CAD treatment ongoing, 6 (42.9%) previously on CAD therapy. At enrollment, among the pts receiving ongoing CAD treatment other than SUT (n=33), the most common treatments were rituximab (15.2%), folic acid derivatives (57.6%), direct factor Xa inhibitors (12.1%) and erythropoietin (12.1%). Among all pts with CAD, the most common treatment prior to enrollment was rituximab either as a monotherapy (33%), or in combination with an antineoplastic agent (1.8%). In the subgroup of pts previously on CAD therapy (n=14), 100% had a history of rituximab treatment; about 50% of pts in the CAD-SUT subgroup and the ongoing CAD treatment subgroup and 33.4% of CAS pts had a history of rituximab use. Rituximab monotherapy was the most prescribed treatment as first or second-line therapy in all subgroups.
Conclusion
In this first interim analysis from the ongoing CADENCE registry, about 50% of enrolled pts with CAD were treatment-naive; among pts with ongoing or history of CAD treatment, the most common treatment prior to enrollment was rituximab, more commonly used as a monotherapy. This initial real-world data on SUT-treated pts is consistent with results from clinical trials, demonstrating the benefit of SUT in managing anemia and hemolysis, and in addressing PROs. Further analyses will provide more insights about the natural history of CAD and CAS and long-term clinical outcomes of SUT.