Contributions
Abstract: PB1866
Type: Publication Only
Background
There is the first evidence of different BCR internalization kinetics of neoplastic cells from the patients with chronic lymphocytic leukemia (CLL) after short-term and long-term administration with ibrutinib.
Aims
We aimed to assess the influence of short-term and long-term ibrutinib treatment on the HLA-DR expression on CLL and T cells.
Methods
The immunophenotyping of CLL and immune cells in peripheral blood was performed in 16 high-risk CLL patients treated with ibrutinib using a flow cytometry.
Results
ur data demonstrated the reduced expression of HLA-DR on CLL cells early after ibrutinib administration (P=0.038) accompanied by an increase in CLL cell counts (P=0.003). In vivo reduction in the HLA-DR expression was confirmed by in vitro culturing of CLL cells with ibrutinib at protein and mRNA levels (P<0.01). The decrease in HLA-DR on CLL cells after the first month of the treatment was followed by the gradual increase of its expression by the 12th month (P=0.016) returning to the levels before initiation of the treatment. The one-month follow-up resulted in elevated absolute counts of CD4+ (P=0.003) and CD8+ (P<0.001) cells which were associated with the increased number of CD4+ and CD8+ cells bearing HLA-DR marker (P<0.001). The long-term administration was associated with increased numbers of CD4+ bearing HLA-DR (P=0.047), along with no changes in CD8+ bearing HLA-DR, CD4+ and CD8+ cell counts, respectively.
Conclusion
Our results provide the first evidence of the time-dependent immunomodulatory effect of ibrutinib on CLL and T cells. The clinical consequences of time-dependent changes in HLA-DR expression in ibrutinib treated patients deserve further investigation.
Grant support: MZ ČR VES16-32339A, IGA_LF_2018_016.
Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical
Abstract: PB1866
Type: Publication Only
Background
There is the first evidence of different BCR internalization kinetics of neoplastic cells from the patients with chronic lymphocytic leukemia (CLL) after short-term and long-term administration with ibrutinib.
Aims
We aimed to assess the influence of short-term and long-term ibrutinib treatment on the HLA-DR expression on CLL and T cells.
Methods
The immunophenotyping of CLL and immune cells in peripheral blood was performed in 16 high-risk CLL patients treated with ibrutinib using a flow cytometry.
Results
ur data demonstrated the reduced expression of HLA-DR on CLL cells early after ibrutinib administration (P=0.038) accompanied by an increase in CLL cell counts (P=0.003). In vivo reduction in the HLA-DR expression was confirmed by in vitro culturing of CLL cells with ibrutinib at protein and mRNA levels (P<0.01). The decrease in HLA-DR on CLL cells after the first month of the treatment was followed by the gradual increase of its expression by the 12th month (P=0.016) returning to the levels before initiation of the treatment. The one-month follow-up resulted in elevated absolute counts of CD4+ (P=0.003) and CD8+ (P<0.001) cells which were associated with the increased number of CD4+ and CD8+ cells bearing HLA-DR marker (P<0.001). The long-term administration was associated with increased numbers of CD4+ bearing HLA-DR (P=0.047), along with no changes in CD8+ bearing HLA-DR, CD4+ and CD8+ cell counts, respectively.
Conclusion
Our results provide the first evidence of the time-dependent immunomodulatory effect of ibrutinib on CLL and T cells. The clinical consequences of time-dependent changes in HLA-DR expression in ibrutinib treated patients deserve further investigation.
Grant support: MZ ČR VES16-32339A, IGA_LF_2018_016.
Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical