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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?

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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

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.


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.


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



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 (

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

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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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. 


CAD, cold agglutinin disease; IgM, immunoglobulin M.


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


CAD, cold agglutinin disease. 


  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 


LDH, lactate dehydrogenase. 


  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 


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


  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


CAD, cold agglutinin disease.


  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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