BASELINE CHARACTERISTICS from the FIRST INTERIM ANALYSIS of CADENCE, the COLD AGGLUTININ DISEASE (CAD) /COLD AGGLUTININ SYNDROME (CAS) REGISTRY.
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All Authors
Michel, M.
Barcellini, W.
Broome, C.M.
Jaeger, U.
Ueda, Y.
Hill, Q.A.
Cid, J.
Wu, J.
Srivastava, S.
Wardecki, M.
LTHT Author
Hill, Quentin
LTHT Department
Oncology
Haematology
Haematology
Non Medic
Publication Date
2024
Item Type
Conference Abstract
Language
Subject
ADULT , ANAEMIA , ANAEMIA, HAEMOLYTIC, AUTOIMMUNE , BONE MARROW , TREATMENT OUTCOME , CLINICAL TRIALS AS TOPIC , CONTROLLED CLINICAL TRIALS AS TOPIC , DIAGNOSIS , COST OF ILLNESS , DRUG THERAPY , FATIGUE , WOMEN , FOLLOW-UP-STUDIES , OUTCOME ASSESSMENT , HAEMOGLOBINS , CLINICAL LABORATORY TECHNIQUES , LYMPHOMA , MEN , MENTAL HEALTH , QUALITY OF LIFE , THROMBOEMBOLISM , VENOUS THROMBOSIS , BILIRUBIN , IMMUNOGLOBULIN G , IMMUNOGLOBULINS , PARAPROTEINS , ANTIBODIES, MONOCLONAL
Subject Headings
Abstract
Background: CADENCE is the first multinational, prospective, longitudinal registry for patients (pts) with cold agglutinin disease (CAD) or cold agglutinin syndrome (CAS). Both are cold-antibody driven autoimmune hemolytic anemias characterized by classical complement pathway-mediated hemolysis, the latter associated with an underlying condition. The objective of CADENCE is to better understand patient demographics, treatment, natural history of disease, long-term clinical outcomes, and disease burden in adult pts. Follow-up will be >=3 years. Aim(s): This first analysis from CADENCE reports baseline (BL) characteristics of enrolled pts. Method(s): Of 140 pts enrolled at time of analysis (data cutoff: Oct. 6, 2023) 133 pts (7 pts excluded: eligibility criteria unmet) were included in the registry: 112 diagnosed with CAD and 21 with CAS. CAD pts are grouped by current treatment status: sutimlimab ongoing (n=15); other CAD treatment ongoing (n=29); treatment-naive (n=49); previously on CAD therapy (n=19). Result(s): At BL (enrollment), most pts were females aged >=65 years, and routine laboratory tests and symptoms of anemia were the most common circumstances for CAD/CAS presentation (Table). Lymphoma/malignancy was the underlying cause in 85.7% (n=18/21) of CAS pts. At BL, monoclonal immunoglobulin (Ig) M was recorded in 74.4% (n=29/39) of CAD and 76.9% (n=10/13) of CAS pts; 89.9% (n=89/99) of CAD and 82.4% (n=14/17) of CAS pts with available measurements had a cold agglutinin titer >1:64. All CAD pts (with available data: n=109) were positive for the C3d direct antiglobulin test (DAT); 75.7% (n=81/107) of pts were negative and 24.3% (n=26/107) weakly positive for the IgG DAT. Normal bone marrow findings were observed in 56.3% (n=36/64) of CAD and 11.8% (n=2/17) of CAS pts. Overall, disease characteristics, laboratory values, and patient-reported outcome (PRO) measures at diagnosis or enrollment demonstrated the burden of disease of CAD. At diagnosis, mean (SD) hemoglobin levels were 9.41 (2.40) g/dL; 47.4% (37/78) of pts reported that the lowest hemoglobin level since diagnosis was <8.00 g/dL. Mean (SD) bilirubin levels were 1.95 (0.83) mg/dL and lactate dehydrogenase levels were 459.10 (218.86) U/L. Before enrollment, 17.0% (n=19/112) of pts had a history of thromboembolic events, most commonly venous thromboembolism. The most common physician-reported symptom at BL was fatigue in 38.4% (n=43/112) of pts. Impact on quality of life (QoL) was assessed using PRO tools. Mean (SD) FACIT-Fatigue scores at BL were 34.93 (12.77) and SF-36 physical and mental component scores were 42.89 (10.50) and 48.03 (11.07), indicating lower QoL than the general population. Prior to enrollment, 50.0% (n=56/112) of pts had received no treatment for CAD and 33.9% (n=38/112) of pts received rituximab. For CAD pts who received treatment, 28.6% (n=32/112) received one line of treatment (LoT), and 21.4% (n=24/112) >=2 LoT. Prior to or at enrollment, 49.1% (n=59/112) of pts had received >=1 transfusion. Similar demographics and BL characteristics were generally observed in the enrolled pts with CAS. Summary/Conclusion This first report from the ongoing CADENCE registry shows that demographics of enrolled CAD pts were consistent with previous literature (predominantly female, >=65 years) and up to 50% of the pts did not receive any specific therapy. However, hemolytic markers, PROs, disease symptoms, and transfusion burden before or at enrollment highlight the disease burden in CAD and CAS. Further analyses will provide insights about the natural history of CAD and CAS and real-world, long-term safety and effectiveness of sutimlimab. (Table present).
Journal
HemaSphere