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2537 Cold Agglutinin Disease (CAD) Real-World Evidence (CADENCE) Registry: Design of the First International, Prospective CAD Registry

Program: Oral and Poster Abstracts
Session: 904. Outcomes Research—Non-Malignant Conditions: Poster II
Hematology Disease Topics & Pathways:
autoimmune disorders, Anemias, Diseases, Immune Disorders, Clinically relevant
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Alexander Röth, MD1, Ulrich Jaeger, MD2, Bernd Jilma3, Wilma Barcellini4*, Anita Hill5*, Quentin Hill5*, David J. Kuter, MD6, Catherine M. Broome7*, Marc Michel8*, Sacha Sergio Zeerleder, M.D.9*, Yasutaka Ueda10*, Jaime Morales-Arias11, Jun Su11 and Sigbjørn Berentsen12*

1Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
2Department of Internal Medicine I, Medical University of Vienna, Vienna, AA, Austria
3Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
4Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
5Department of Haematology, St James’ University Hospital, Leeds, United Kingdom
6Hematology Division, Massachusetts General Hospital, Boston, MA
7Division of Hematology, MedStar Georgetown University Hospital, Washington, D.C.
8Henri-Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, UPEC, Paris, France
9Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
10Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan
11Sanofi, Cambridge, MA
12Department of Research and Innovation, Haugesund Hospital, Haugesund, Norway


Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia in which hemolysis is mediated via the classical complement pathway. Its estimated incidence rate is 1 per 1 million persons per year, with a prevalence of 16 cases per 1 million persons. Patients with CAD can experience debilitating fatigue and poor quality of life (QoL), and they may have an increased risk of thromboembolism and early mortality. Owing to the rarity of the disease, information regarding the natural history of this condition and its long-term impact and complications is sparse (Jäger et al. Blood Rev. 2019). The rationale and design of a large, international database of patients with CAD is presented.


CADENCE is a multinational, multicenter, observational, prospective, longitudinal registry. Patients ≥18 years of age with primary CAD, secondary CAD/cold agglutinin syndrome, and mixed warm and cold autoimmune hemolytic anemia will be included. The main objective of this registry is to better understand various aspects of CAD, including patient and clinical characteristics, patterns of CAD treatment use, healthcare resource utilization (HRU), natural history of disease, long-term clinical outcomes, and impact on patient QoL. The enrollment period is expected to last ≥2 years, and patients will be followed for 3 years after enrollment. Data will be collected and analyzed at regional and global levels; sites will complete electronic case report forms, and patients will complete patient-reported outcome (PRO) questionnaires (36-Item Short Form Health Survey [version 2] and Functional Assessment of Chronic Illness Therapy-Fatigue scale) at enrollment and at intervals of about every 6 months during follow-up.


The CADENCE Registry was launched in December 2019, with last patient last visit expected at the end of 2024. It is expected to enroll approximately 725 patients with CAD across 121 sites in multiple countries, including the United States, Canada, France, United Kingdom, Italy, Germany, Austria, Norway, Japan, Australia, and Spain (Figure). Data collected will include clinical characteristics, disease complications (eg, thromboembolism), comorbidities, mortality, treatment regimens, HRU, and PROs. Relevant biomarkers will be assessed. Interim analyses will be performed after 100 patients, 250 patients, and 500 patients are enrolled in the study. Final analyses will be performed at the end of the study both at regional and global levels.


As the first global registry for patients with CAD, CADENCE will help advance the understanding of the natural history and disease process of this ultra-rare disease for which the ability to conduct prospective trials with sufficient numbers of patients is challenging. This registry will provide clinicians with a data resource that may help improve treatment practices for patients with CAD.

Disclosures: Röth: Apellis: Consultancy, Honoraria; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Biocryst: Consultancy, Honoraria. Jaeger: Novartis: Consultancy, Honoraria, Research Funding; CDR Life AG: Consultancy, Research Funding; Miltenyi: Consultancy, Honoraria; Takeda: Honoraria; Infinity: Honoraria; Gilead: Honoraria, Research Funding; True North: Honoraria, Research Funding; Amgen: Honoraria; F. Hoffmann-La Roche: Honoraria, Research Funding; AbbVie: Honoraria; Karyopharm: Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding. Jilma: True North Therapeutics: Consultancy, Other: reimbursement for travel costs for scientific presentations; Bioverativ: Consultancy, Other: reimbursement for travel costs for scientific presentations. Barcellini: Incyte: Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Other: invited speaker , Research Funding; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: invited speaker , Research Funding. Hill: Alexion Pharmaceuticals Inc.: Current Employment. Kuter: Dova: Consultancy, Honoraria; Takeda (Bioverativ): Consultancy, Honoraria, Other, Research Funding; Principia Biopharma: Consultancy, Honoraria, Other, Research Funding; Protalex: Consultancy, Honoraria, Research Funding; Rigel: Consultancy, Honoraria, Other, Research Funding; Zafgen: Consultancy, Honoraria; Sanofi (Genzyme): Consultancy, Honoraria; Shionogi: Consultancy, Honoraria; Up-To-Date: Consultancy, Honoraria, Patents & Royalties; UCB: Consultancy, Honoraria; Platelet Disorder Support Association: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Kezar Life Sciences, Inc: Other, Research Funding; Protalex: Consultancy, Honoraria, Other, Research Funding; Merck Sharp Dohme: Consultancy, Honoraria; Kyowa-Kirin: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Shionogi: Consultancy; Novartis: Consultancy, Honoraria; Immunovant: Consultancy, Honoraria; Momenta: Consultancy, Honoraria; Protalix Biotherapeutics: Consultancy; Principia: Consultancy, Research Funding; Shire: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria; Actelion (Syntimmune): Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Daiichi Sankyo: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Agios: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Alnylam: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Caremark: Consultancy, Honoraria; Immunovant: Other: Travel Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Argenx: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; CRICO: Consultancy, Honoraria. Broome: Alexion Pharmaceuticals, Inc: Honoraria, Research Funding; Cellphire: Honoraria, Research Funding; Bioverativ: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Rigel: Honoraria, Research Funding; Sanofi Genzyme: Honoraria, Research Funding. Michel: Bioverativ: Consultancy; Rigel: Consultancy; Alexion Pharmaceuticals: Consultancy. Ueda: Sanofi: Consultancy, Honoraria; Alexion: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Other: All authors received support for third-party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.; Novartis: Honoraria; Chugai: Research Funding. Morales-Arias: Sanofi: Other: Employee at time of study. Su: Sanofi: Current Employment. Berentsen: Alexion, Apellis, Bioverativ, Janssen-Cilag, True North Therapeutics: Honoraria; Alexion, Apellis, Bioverativ and Janssen-Cilag: Other: Travel grants ; Apellis, Bioverativ, Momenta Pharmaceuticals and True North Therapeutics: Consultancy; Mundipharma: Research Funding.

*signifies non-member of ASH