CLL Society interview - Dr. Shahzad Mustafa on What it Means to be Immunocompromised for Patients with CLL/SLL January 13, 2023

[lankisterguy]

Dr. Shahzad Mustafa on What it Means to be Immunocompromised for Patients with CLL/SLL January 13, 2023 cllsociety.org/2023/01/dr-s...

youtu.be/DSOKTmffc-s(Not working as expected?)

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In this interview, Dr. Brian Koffman spoke with Dr. Shahzad Mustafa, Division Chief of Allergy, Immunology, and Rheumatology at Rochester Regional Health and Clinical Associate Professor of Medicine at the University of Rochester School of Medicine and Dentistry. They discussed immune deficiency (a.k.a. being immunocompromised) and what that means for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

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What does it mean to be immune deficient or immunocompromised?

Immune deficiency is a broad term, but it means your body cannot fight off infections effectively. Some of the most clinically significant immune problems are seen in individuals who have trouble making antibodies. This can be caused by certain genetic conditions, certain medications, and certain cancers such as CLL/SLL. CLL and SLL are cancers of the B cells, which are the immune cells that produce antibodies. This means that your B cells have a more challenging time making functional antibodies, and your risk of infection is higher.

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How does this change the response to vaccines?

Vaccination is the cornerstone of infection prevention, whether against tetanus or COVID-19. However, patients with CLL/SLL have suboptimal vaccination responses because the ability of B-cells to make antibodies is impaired. So it’s not nothing, but it is also not a complete normal response.

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What are T cells, and how are they different in CLL/SLL?

T cells are another type of immune cell that can directly kill infected cells or help coordinate the immune response to a pathogen. They are a bit harder to measure than B cells, so we don’t know quite as much about their function in CLL/SLL. However, T cells in CLL/SLL patients are said to be “exhausted” and don’t respond to bugs as well as in normal individuals. Some treatments, such as ibrutinib, can raise T cell numbers.

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Are all patients with CLL/SLL immune deficient?

Yes, even patients who have just been diagnosed and never received treatment have some degree of immune dysfunction. This is not surprising given that CLL/SLL is a cancer of the B cells, which are a critical part of the immune system. In addition, some therapies can further deplete immune function and antibody levels.

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How do monoclonal antibody therapies like rituximab and obinutuzumab affect the immune response?

Anti-CD20 monoclonal antibodies like rituximab and obinutuzumab are commonly used therapies for treating CLL/SLL. They target the CD20 protein that is expressed on the surface of all B cells. So while they help eliminate many malignant B cells, they also further impair antibody production because they deplete B cells. Therapies like this are appropriate for treating B cell cancers, but they reduce the body’s ability to make antibodies, respond to vaccinations, and fight off infections.

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Are there ways to reboot the immune system?

For patients who cannot make enough or cannot make functional antibodies, antibody infusions such as intravenous immunoglobulin are available. Bone marrow transplant (a.k.a. stem cell transplant) is probably the best way to reboot the immune system when patients have blood cancers, but bone marrow transplant is not currently indicated for most patients with CLL/SLL. In addition, its role has been shrinking with the introduction of more effective targeted therapies.

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Any final thoughts?

It’s vital for patients with CLL/SLL to be aware that they likely have some degree of immune deficiency, and there is routine clinical bloodwork to evaluate this that can be checked at any time during the disease. Being aware of immune deficiency can also help patients take common sense precautions to minimize the risk of infections.

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Please enjoy this brief interview with Dr. Mustafa.

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

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Len

[Iupiter]

Thank you Len! Great interview.

Do you know which blood tests Dr Mustafa refered to can give us an idea of the degree of immune deficiency a person may have?

Thank you

[lankisterguy Volunteer in reply to Iupiter]

Hi lupiter

The most common measure is IGG, IGA & IGM which may give a general indication of the levels of humoral immunity (sciencedirect.com/topics/ag... , but can only be supplemented with IVIG infusions that last 4-6 weeks.

Also monitoring Neut# / ANC - levels below 1.0 can indicate a susceptibility to sepsis and other fast & dangerous infections.

my.clevelandclinic.org/heal...

Len

[sheilamarie]

"Commonsense precautions to minimize infections": masks, washing hands, keeping 6 feet away from others, vaccinations, but are there other steps we can take that I'm not aware of? Speaking as one who has had numerous infections the past year, and now, and who follows the precautions I've mentioned. Thank you.

[lankisterguy Volunteer in reply to sheilamarie]

Hi sheilamarie,

I would suggest using the best fitting N95/FFP2 respirator (mask) and carefully choosing where and how long to have it off for eating and drinking (the shortest time and fewest people is best).

Honeywell Surgical N95 Respirator, Safety NIOSH-Approved, 20-pack (DC365N95HC)

3M Particulate Respirator 8577, P95, with Nuisance Level Organic Vapor Relief (Pack of 10)

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And if you are having frequent infections negotiate with your medical team to get IVIG or SubQIG igliving.com/life-with-ig/t...

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Len

[sheilamarie]

Thank you so much for your informative reply, lankisterguy. My oncologist recommends infusions only if one is hospitalized for infections; so far, antibiotics are working for me, no hospitalizations. I appreciate the article you linked - I learned a lot about this topic. My recent numbers for tested immunoglobulin are: IGA 104, IGG 471, IGM 47. IGG only half of what it should be, the others little bit higher than baseline. I think I'll start putting more emphasis on diet - again! And getting a better mask. By the way, I'm on one ibrutinib 5 days/week, 140mg capsule and all blood numbers very good. Again, much gratitude for answering my question.