AIM Test Could Help Predict COVID-19 Vaccine Response in Patients With CLL

Patients with chronic lymphocytic leukemia (CLL) may not be fully protected after vaccination, and some are at higher risk of severe COVID-19 infection due to poor T-cell responses. Researchers found that CD4 and CD8 memory responses were impaired 6 to 8 months postvaccination, with CD8 responses influenced by treatment type. These findings could help refine vaccination strategies for immunocompromised patients.

3D illustration of T-cells | Image Credit: © Emile - stock.adobe.com

More than 23,000 people in the US are anticipated to receive a diagnosis of CLL, the most prevalent form of leukemia in adults, in 2025 alone. It is characterized by the gradual growth of clonal mature B lymphocytes, which results in weakness or exhaustion, fever and infection, or easy bruising or bleeding, as well as painless swelling of the lymph nodes in the neck, underarm, stomach, or groin. CLL also causes weakened immune function, impairing normal functions of the immune system as well as affecting responses to vaccines.¹

Evidence has shown that patients with hematologic malignancies (HM), such as CLL, have more severe outcomes and increased fatality rates following COVID-19 infection. In patients with HM, COVID-19 causes reduced antibody production that impairs humoral response. Patients with CLL who were vaccinated present with reduced humoral responses to vaccines, particularly those treated with Bruton tyrosine kinase inhibitors, such as ibrutinib (Imbruvica; Janssen Biotech, Inc.).²

To identify patients eligible or ineligible for vaccination, the researchers evaluated T-cell-mediated responses to COVID-19 vaccines, primarily focusing on CD4+ and CD8+ T-cell memory response. This was done through assessment of peripheral blood mononuclear cells (PBMCs) were isolated from CLL patients (n = 42) and healthy controls (HC; n = 33) using the AIM test. Participants were enrolled 6 to 8 months following the second dose of the BNT162b2 mRNA COVID-19 vaccination.²

In the study, all HCs exhibited a CD4+ T cell memory response, whereas 28.6% of patients with CLL failed to respond. CD8+ T cell memory response was impaired in 61.9% of CLL patients compared with 33.3% of HC. Additionally, even among CLL patients who did respond, the magnitude of the CD8+ memory response was significantly reduced. Notably, impairment in CD4+ AIM+ memory was linked to more severe COVID-19 infections.²

The study also found that ibrutinib therapy negatively affected IL-2 production by CD8+ cells, though longer treatment duration was associated with improved memory response. Given the poor vaccine response in most CLL patients, these findings highlight the AIM test as a promising tool for identifying non-responders and evaluating immune protection.²

Unlike cytokine-based methods, which have limitations, the AIM assay is more sensitive and can better identify different T cell subpopulations and their responses; however, its use in clinical settings faces challenges, including high costs, the need for specialized equipment, and inconsistent protocols across labs. Standardized guidelines are needed to improve its reliability.²

Despite these obstacles, ongoing advancements in automation, cost reduction, and standardization could help integrate AIM testing into routine practice. This research contributes to a better understanding of how well vaccines work in immunocompromised patients and could one day help identify those at high risk for severe infections, allowing for earlier interventions and personalized treatment strategies.

REFERENCES

1. Regulating cholesterol may enhance T-Cell function in patients with chronic lymphocytic leukemia. Pharmacy Times. March 14, 2025. Accessed March 26, 2025. https://www.pharmacytimes.com/view/regulating-cholesterol-may-enhance-t-cell-function-in-patients-with-chronic-lymphocytic-leukemia

2. Raineri D, Mazzucca C, Moia R, et al. Impairment of the T cell memory response in chronic lymphocytic leukemia patients after SARS-CoV-2 vaccination. Vaccine. January 18, 2025. doi.org/10.1016/j.vaccine.2025.126723