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    Faculty & Disclosures
    Prof. Morie Gertz

    Mayo Clinic, Rochester, Minnesota, USA

    Morie Gertz, MD, is the Roland Seidler Jr. Professor of the Art of Medicine, and Chair Emeritus of the Department of Internal Medicine, at the Mayo Clinic in Rochester, Minnesota, USA. read more

    Prof. Gertz has served as chair of the Division of Haematology and chair of the Department of Medicine at the Mayo Clinic in Rochester. He was the first treasurer of the International Society of Amyloidosis, and the International Myeloma Society. 

    Prof. Gertz has authored over 1,000 peer reviewed publications and over 90 book chapters. He serves on the editorial boards of Amyloidosis, Acta Haematologica and Clinical Lymphoma & Myeloma. He is co-editor of Neoplastic Diseases of the Blood. In 2019, the Department of Medicine awarded him its lifetime research achievement award. In 2021, he was appointed chair of the committee for the hematology certification examination for the American Board of Internal Medicine.

    Prof. Morie Gertz discloses: Advisory board/panel fees from AbbVie, Aptitude, Ashfield, Celgene, Ionis/Akcea, Janssen, Johnson & Johnson, Prothena, Sanofi and Sorrento. Grants/research support from: Ashfield and Juno.
    Prof. Bernd Jilma

    Medical University of Vienna, Vienna, Austria

    Bernd Jilma, MD, holds a tenure position as Professor for Internal Medicine and Clinical Pharmacology at the Medical University of Vienna, Austria. read more

    For almost 30 years, Prof. Jilma has worked in the field of clinical pharmacology. He has served on various regulatory committees of the European Medicines Agency and was the Austrian delegate and member of the Committees of Orphan Medicinal Products (COMP), the Scientific Advice Working Party (SAWP), and the Committee for Advanced Therapies (CAT). 

    His early research career focused on evaluating anticoagulants in endotoxemia-driven coagulation. Prof. Jilma identified potentially detrimental drug interactions of morphine and platelet function inhibitors. Early clinical phase I/II trials with an aptamer directed against von Willebrand factor provided proof of concept for the treatment of thrombotic thrombocytopenic purpura. This encouraged further development of a biologic (nanobody) directed against the same target, which eventually led to the marketing approval of caplacizumab. Prof. Jilma also designed the phase I–III trials which led to marketing authorization of the C1s complement inhibitor sutimlimab for the treatment of cold agglutinin disease. 

    Prof. Jilma has authored more than 500 papers in peer-reviewed international journals including New England Journal of Medicine, Lancet and Blood.

    Prof. Bernd Jilma discloses: Advisory board/panel and speaker’s bureau fees from Sanofi.
    Dr Shirley D'Sa

    University College London Hospitals, London, UK

    Shirley D’Sa, MD, FRCP, FRCPath, is a haematologist and Associate Professor at University College London Hospitals (UCLH) NHS Foundation Trust in London, UK, where she also completed her specialist training in haematology. read more

    Dr D’Sa specialises in the management of patients with IgM-related conditions and paraproteinaemic neuropathies.

    She is clinical lead for the UCLH Centre for Waldenström’s macroglobulinemia (WM) and Related Disorders, and haematological lead in the Joint Neurohaematology Service alongside the neurology lead, Prof. Michael Lunn at the National Hospital for Neurology, Queen Square, in London.

    Dr D’Sa is a chief/principal investigator in several clinical trials in Waldenstrӧm’s macroglobulinemia (WM) and cold agglutinin disease (CAD) and is a committee member on the International Workshop on WM, and the British Society for Haematology Guidelines Group.

    Dr D’Sa is a co-trustee with patients and colleagues in the UK Registered Charity, WMUK and the chief investigator for the Rory Morrison WMUK Registry project and associated conditions, which has more than 1,100 patients registered from several centres across the UK. She is also a member of the Medical Advisory Panel of Lymphoma Action in the UK.

    Dr Shirley D’Sa discloses: Advisory board/panel fees from BeiGene, Janssen and Sanofi. Consultancy fees from BeiGene and Sanofi. Grants/research support and speaker’s bureau fees from BeiGene.
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    touchPANEL DISCUSSION
    A visually engaging discussion designed to emulate a ‘live’ panel experience and provide clinicians with practical expert insights to address their clinical challenges. Useful tips below will show how to navigate the activity. Close

    Understanding the immunopathogenesis of CAD: What are the implications of new and emerging therapies?

    Faculty Podcast Featured
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    Learning Objectives

    After watching this activity, participants should be better able to:

    • Describe the immunopathogenesis of cold agglutinin disease (CAD) and implications for effective patient management
    • Appraise current and emerging treatment options for patients with CAD using the latest data
    • Evaluate strategies to individualize the treatment and management of patients with CAD
    Overview

    In this activity, three experts discuss the pathogenesis of cold agglutinin disease (CAD) and consider the current diagnostic pathway and differential diagnoses, as well as the role of complement inhibitors as an emerging treatment option for patients with primary CAD. The discussion is guided by pre-canvassed questions provided by the haematological clinical community.

    This activity is jointly provided by USF Health and touchIME. read more

    Target Audience

    This activity has been designed to meet the educational needs of haematologists and haematologist-oncologists involved in the management of cold agglutinin disease.

    Disclosures

    USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity.  The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

    Faculty

    Prof. Morie Gertz discloses: Advisory board/panel fees from AbbVie, Aptitude, Ashfield, Celgene, Ionis/Akcea, Janssen, Johnson & Johnson, Prothena, Sanofi and Sorrento. Grants/research support from: Ashfield and Juno.

    Prof. Bernd Jilma discloses: Advisory board/panel and speaker’s bureau fees from Sanofi.

    Dr Shirley D’Sa discloses: Advisory board/panel fees from BeiGene, Janssen and Sanofi. Consultancy fees from BeiGene and Sanofi. Grants/research support and speaker’s bureau fees from BeiGene.

    Content reviewer

    Caitlin Papa, MSN, APRN-C has no financial interests/relationships or affiliations in relation to this activity.

    Touch Medical Directors

    Kathy Day and Sadaf Kazi have no financial interests/relationships or affiliations in relation to this activity.

    USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

    Requirements for Successful Completion

    In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

    If you have questions regarding credit please contact cpdsupport@usf.edu.

    Accreditations

    Physicians

    This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

    USF Health designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

    Advanced Practice Providers

    Physician Assistants may claim a maximum of 0.75 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

    The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

    Date of original release: 05 October 2022. Date credits expire: 05 October 2023.

    If you have any questions regarding credit please contact cpdsupport@usf.edu.

    This activity is CE/CME accredited

    To obtain the CE/CME credit(s) from this activity, please complete this post-activity test.

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    Haematology / Immunotherapy
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    This Activity Is Funded By:

    An independent medical education grant from Sanofi and is jointly provided by USF Health and touchIME.

    The information provided by this CE activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

    USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

    USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CE to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

    Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

    This content is intended for healthcare professionals.

    Date of original release: 05 October 2022. Date credits expire: 05 October 2023.

    Claim Credit
    touchPANEL DISCUSSION
    Understanding the immunopathogenesis of CAD: What are the implications of new and emerging therapies?
    0.75 CE/CME credit
    Question 1/5
    Which of the following statements best reflects current understanding of the pathogenesis of primary CAD?

    CAD, cold agglutinin disease; IgG, immunoglobulin G; IgM, immunoglobulin M.

    CAD results from cold agglutinin IgM antibodies produced by a clonal B-cell population. The cold agglutinins then target red blood cells, activating the complement cascade to cause mostly extravascular haemolysis. 

    Abbreviations

    CAD, cold agglutinin disease; IgM, immunoglobulin M.

    Reference

    Berentsen S. Front Immunol. 2020;11:590.

    Question 2/5
    Your symptomatic patient with CAD requires treatment and has asked about their options. What would you tell them about the efficacy outcomes achieved with the C1s complement inhibitor sutimlimab in the phase III CARDINAL and CADENZA trials?

    C, serum complement protein; CAD, cold agglutinin disease.

    The phase III CARDINAL and CADENZA trials investigated sutimlimab as a treatment for CAD.1,2 In both trials, patients treated with sutimlimab had maintained improvements in haemoglobin levels over 26 weeks and showed reduced bilirubin levels. Sutimlimab was also able to rapidly inhibit the complement pathway in both CARDINAL and CADENZA.1,2

    Abbreviation

    CAD, cold agglutinin disease. 

    References

    1. Röth A, et al. N Engl J Med. 2021;384:1323–34.
    2. Röth A, et al. Blood. 2022;140:980–91.
    Question 3/5
    What biomarkers may be useful to monitor disease progression or treatment effectiveness?

    CAD, cold agglutinin disease; LDH, lactate dehydrogenase.

    Haemoglobin is an important marker of haemolysis as the most direct indicator of clinical severity. Haemoglobin should be monitored in all patients as an indicator of treatment response.1 Elevated LDH can indicate haemolysis, and levels decrease with a reduction in haemolysis.1 Bilirubin also increases with haemolysis and normalises with recovery.1 Haptoglobin is usually decreased or absent in haemolysis.2 A decreased reticulocyte count may indicate haemolysis. However, reticulocytosis can be a sign of recovery, with reticulocytes remaining elevated for several days until haemoglobin levels are restored.1 

    Abbreviation

    LDH, lactate dehydrogenase. 

    References

    1. Barcellini V, Fattizzo B. Dis Markers. 2015;635670.
    2. Jäger U, et al. Blood Rev. 2020;41:100648.
    Question 4/5
    Your elderly patient presents in an emergency situation with signs of acute haemolysis and requires prompt treatment. What treatment would you recommend to limit further haemolysis in this patient?

    Sutimlimab, a C1s inhibitor, has shown to inhibit the complement pathway and improve signs of haemolysis in patients with CAD in phase III clinical trials within one to three weeks.1,2 While rituximab is a well-established treatment, response times are long.3 Plasmapheresis has also been used as a rapid-acting rescue therapy; however, it is a labour intensive process, making it not an ideal option and should be considered a last-resort therapy.3 Corticosteroids are not considered effective and are not recommended for CAD.3 

    Abbreviations

    C, serum complement protein; CAD, cold agglutinin disease.

    References

    1. Röth A, et al. N Engl J Med. 2021;384:1323–34.
    2. Röth A, et al. Blood. 2022;140:980–91.
    3. Jäger U, et al. Blood Rev. 2020;41:100648.
    Question 5/5
    In order to best manage patient expectations, what ongoing symptoms and complications should be discussed with patients who have CAD and are receiving rituximab +/- chemotherapy?

    CAD, cold agglutinin disease.

    Retrospective, real-world data demonstrated that patients with CAD have a high risk of hospitalization1 and often still experience anaemia despite treatment.2 A large retrospective cohort trial also identified a 1.9 times higher risk of a thromboembolic event in patients with CAD compared with patients without CAD.3

    Abbreviation

    CAD, cold agglutinin disease.

    References

    1. Wilson A, et al. Presented at the ASH Annual Meeting, 5–8 December 2020. Abstract 151.
    2. Mullins M, et al. Blood Adv. 2017;1:839–48
    3. Broome C, et al. Res Pract Thromb Haemost. 2020;4:628–35.
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    This Activity Is Funded By:

    An independent medical education grant from Sanofi and is jointly provided by USF Health and touchIME.

    The information provided by this CE activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

    USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

    USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CE to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

    Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

    This content is intended for healthcare professionals.

    Date of original release: 05 October 2022. Date credits expire: 05 October 2023.

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