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).
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, medications, and 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, so your risk of infection is higher.
How does being immunocompromised change the response to vaccines?
Vaccination is the cornerstone of infection prevention, whether against tetanus, COVID-19, or other infections. However, patients with CLL / SLL have suboptimal vaccination responses because the ability of B-cells to make antibodies is impaired. So it’s not that those who are immunocompromised never respond to vaccines, but it is typically not a completely normal or robust response.
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” so they don’t respond to infections as well as they do in those individuals with fully functional immune systems. Some treatments, such as ibrutinib, can raise T cell numbers.
Are all patients with CLL / SLL immune deficient?
Yes, even patients who have just been diagnosed and have 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 for CLL / SLL can further deplete immune function and antibody levels.
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 the total number of B cells available to help fight off infection. 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.
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.
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 available to evaluate this that can be checked at any time during the disease. Having an awareness of the immune deficiency that comes alongside a CLL / SLL diagnosis is important because it highlights the importance of taking the additional common sense infection control precautions required to minimize the risk of infections.
Please enjoy this brief interview with Dr. Mustafa.
Take care of yourself first.
Ann Liu, PhD