CLL-050 Induction of Neutralizing Antibodies in Chronic Lymphocytic Leukemia Patients After SARS-CoV-2 mRNA Vaccination: A Monocentric Experience

Background: SARS-CoV-2 infection increases the clinical risk and mortality of patients with chronic lymphocytic leukemia (CLL). Covid-19 vaccinations have the potential to protect individuals from severe infection, but little is known about the antibody response profile in these patients after vaccination. We compared the anti-receptor binding domain (RBD) and neutralizing antibody responses of 27 patients with CLL to those of healthy donors after mRNA Covid-19 vaccination. Methods: Of the 27 patients enrolled in the study, 21 received the BNT162b2 mRNA vaccine and 6 received the Spikevax mRNA vaccine. Four patients were in clinical remission after treatment, 10 were treatment-naïve, and 13 were under treatment at the time of vaccination. Blood samples were taken before vaccination and after the second dose, with a median time between of 23 days. The levels of anti-RBD IgG, IgM, and IgA were evaluated by ELISA on recombinant RBD; the neutralizing antibody response was evaluated by spike protein inhibition assay (SPIA). We also performed a fluorescence-activated cell sorting study of peripheral blood mononuclear cell subpopulations, a disease burden assessment using blood indicators (lactate dehydrogenase, beta-2-microglobulin, lymphocytic count) and imaging, and an evaluation of IgG levels at the time of vaccination. Results: A comparison of anti-RBD antibody seroconversion (IgG, IgM, and IgA) and neutralizing antibodies present after vaccination between 27 patients with CLL and healthy control subjects indicated that CLL patients had a considerably lower response rate (50% vs. 100%) and lower antibody levels than the healthy controls. We found an inverse correlation between the spleen dimension and lymphonodal area. By stratifying patients according to the presence of neutralizing antibodies after vaccination, we found a larger prevalence of SPIA positives than SPIA negatives in treatment-naïve patients (60%); however, patients undergoing treatment had a much lower percentage of SPIA positives (23.1%). Conclusions: Only around half of vaccinated CLL patients acquire detectable anti-RBD and neutralizing antibodies, according to our findings. Furthermore, we discovered a substantial difference in the rates of detectable anti-SARS-CoV-2 antibodies between patients who were treatment-naïve/in clinical remission and those on CLL-directed treatment. The persistence and burden of disease represent a surrogate of vaccine failure, probably due to the persistence of immune dysfunction.