Poster: CLL-189 Ibrutinib Treatment and Its Impact on Circulating Immune Cells in Chronic Lymphocytic Leukemia Patients

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy characterized by immune dysregulation, infections represent a cause of mortality and morbidity in CLL. Ibrutinib is a Bruton's tyrosine kinase inhibitor very effective on CLL, but this treatment is burdened by infective complications, especially within the first months of therapy. The decline of infections could suggest that immune competence may be restored by Ibrutinib directly or by reductions in CLL burden.This monocentric prospective study evaluates immunophenotypic changes in circulating immune cells in CLL patients treated with Ibrutinib. We collected peripheral blood samples at baseline, 3, and 6 months of therapy; new samples at 12 and 24 will be collected.Data of 20 patients treated with Ibrutinib in our Centre since January 2021 were collected. Multiparametric flow cytometry was used to characterize immune cells. Median age at Ibrutinib start was 74 years. Nine patients were treatment-naive, 7 were on second-line. The other 4 have already received at least 2 previous therapy lines. In particular, 11 have received chemoimmunotherapy (CIT).The only correlation between clinical-biological data and impact on baseline cells was found between previous exposure to CIT and CD3+HLA-DR+cells (median 1×109/L vs 6×109/L in chemo-naïve patients, p=0.025). No differences in who have received a chemo-free therapy prior to Ibrutinib or based on the number of previous therapy lines. After 6 months of therapy, we observed statistical differences between baseline for CD19+decrease (31×109/L vs 11<109/L, p=0.04). Another difference was found in the decrease of CD3+CD4+count (1×109/L vs 0.76×109/L, p=0.04). Also, the CD3+ count decreased after 6 months (1.7×109/L vs 1.55×109/L, p=0.04). The last significant difference was in the decrease of NK cells (0.5×109/L vs 0.02×109/L, p=0.04). Infectious complication was observed in 8 patients (40%). Specifically, 4 patients experienced COVID-19, 4 pneumonia and one experienced both and a complicated urinary tract infection.These preliminary data show an early reduction of CD4+T-cell subset, dysfunctional in CLL. NKT cells, that mediate tumor immunosurveillance, at baseline were higher than expected but with Ibrutinib they decreased by 59% in 6 months. Further data are needed, but these suggest an impact of Ibrutinib on the immune system that could help on infections.