Improving Quality of Life for Immunocompromised CLL Patients

Written by Dr. Kaique Filardi

Chronic lymphocytic leukemia (CLL) invariably compromises the immune system, leading to varying degrees of immunodeficiency in all patients. The disease disrupts multiple immune pathways, manifesting as both leukemia-related immunodeficiency — affecting humoral and cellular immune functions — and treatment-induced immunosuppression. 

Specifically, cumulative immune suppression occurs as a consequence of therapies targeting CLL, such as chemoimmunotherapy. This dual impact on the immune system significantly heightens patients’ susceptibility to infections and other complications, underlining the importance of vigilant monitoring and tailored immunological support throughout the disease course.

Dr. Adam Kittai, Associate Professor of Medicine at Mount Sinai in New York, tells SurvivorNet Connect that improving patient quality of life involves a bit of a balancing act. 

“When we start therapy, even though some of our therapies also lead to an immunocompromised state, they also affect the disease, meaning they dampen down the disease, allowing the immune system to recuperate and function a little bit more. So there’s this kind of balance between the disease being affected by the drug, allowing for the immune system to kick back in, and the actual drug affecting the immune system,” he says.

Proactive monitoring of patients at risk for immunodeficiency, particularly those undergoing conventional immunosuppressive treatments or newer, targeted therapies, is essential. Early identification of these individuals allows for timely intervention, potentially preventing the development of severe infections. By closely tracking immune function, clinicians can adjust therapeutic strategies to mitigate risks and improve patient outcomes, ensuring more effective management of immunosuppression-related complications.

Boosting Immune Defense in CLL

Vaccination

Patients with CLL consistently exhibit a diminished and less sustained response to vaccinations. Factors that contribute to this weakened vaccine efficacy include advanced stages of the disease, older age, and the presence of hypogammaglobulinemia. These characteristics compromise the immune system’s ability to mount a robust defense, making it essential for clinicians to consider alternative preventive strategies or tailored vaccination approaches to protect this vulnerable population from infections. 

These patients should be administered non-live vaccines at diagnosis, when their immune system is least compromised by the disease and before the effects of subsequent therapies. Early vaccination maximizes the likelihood of a more effective immune response, offering critical protection before further immunosuppression occurs due to disease progression or treatment. 

“The other thing that we do also is make sure that our patients receive is vaccines … I make sure that my patient gets their pneumonia shots and they get it every five years. I make sure that they’re up to date on their COVID-19 vaccinations as well as getting their flu shots yearly. And we also have a discussion about shingles and RSV as well,” explains Dr. Kittai. 

Additional strategies to improve vaccine efficacy in patients with CLL include the co-administration of immunomodulatory drugs and the use of booster doses. These approaches aim to amplify the immune response, compensating for the weakened immunity seen in CLL patients. By enhancing vaccine effectiveness, these interventions may provide better protection against infections, offering a crucial advantage in managing the long-term health of individuals with CLL.

Immunoglobulin Replacement 

The primary treatment for addressing hypogammaglobulinemia in patients with CLL is the exogenous administration of purified IgG, sourced from pooled donor plasma. This therapeutic approach replenishes deficient immunoglobulins, bolstering the patient’s immune defense and reducing the risk of infections. 

Regular IgG supplementation plays a critical role in managing the immunodeficiency associated with CLL, particularly in those who are highly susceptible to recurrent infections due to low antibody levels.

The risk of infection in patients with CLL tends to rise when IgG levels drop below 6 g/L. One study found that two-thirds of infections occurred in a quarter of patients whose IgG levels were below 3 g/L. 

“If [patients are] having recurrent viral infections, which is typically upper respiratory tract infections, I always test for IgG levels and if patients have an IgG less than 500, I’m very proactive about giving them IVIG monthly. That usually will help in preventing further upper respiratory tract infections, especially during the winter,” Dr. Kittai explains.

Investigations into immunoglobulin replacement therapy have evaluated doses ranging from 100 to 800 mg/kg, administered intravenously every 3 to 5 weeks. In a comparative study, it was determined that a regimen of 400 mg/kg every 3 weeks for 4 doses, followed by maintenance therapy every 5 weeks, provided the optimal balance of infection prevention and treatment efficacy.

IgG replacement therapy is generally well-tolerated, with most patients experiencing only mild systemic reactions, such as local irritation at the injection site during subcutaneous administration. However, intravenous administration has been linked to rare but significant adverse effects, including anaphylactoid reactions and an elevated risk of thromboembolic events. 

“I usually give it for a full year, and if someone’s IgG levels are able to get back up above 500, I may pause that IVIG monthly for the summer months to allow the patients to have some sort of break, and then we’ll reinitiate it back during the winter months when we know that upper respiratory tract infections by virus is typically to be the highest,” Dr. Kittai tells SurvivorNet Connect. 

Despite these potential risks, IgG therapy remains a vital component of managing hypogammaglobulinemia in CLL, particularly when appropriately monitored and tailored to the individual patient’s needs.

“So, I think I want to encourage my community practice doctor colleagues to make sure that their patients with CLL are up to date on their vaccines and that they’re looking for low IgG levels in order to give them back IVIG,” Dr. Kittai adds.