Dynamic changes in HLA-DR expression during short-term and long-term ibrutinib treatment in patients with chronic lymphocytic leukemia. (September 2018)

• Record Type: Journal Article
• Authors: Manukyan, Gayane; Turcsanyi, Peter; Mikulkova, Zuzana; Gabcova, Gabriela; Urbanova, Renata; Gajdos, Petr; Smotkova Kraiczova, Veronika; Zehnalova, Sarka; Papajik, Tomas; Kriegova, Eva
• Is Part Of: Leukemia research. Volume 72(2018)
• Page Start: 113
• Page End: 119
• Publication Date: 2018-09
• Subjects: Chronic lymphocytic leukemia -- Ibrutinib -- HLA-DR -- CLL cells -- T cells; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2018.08.006
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: Ibrutinib influences the expression of HLA-DR on CLL cells. Ibrutinib gradually increases HLA-DR levels on circulating monocyte subsets. Immunomodulatory effect of ibrutinib on CLL, T cells, monocytes is time-dependent. Abstract: There is the first evidence of changes in the kinetics of B cell antigen receptor (BCR) internalisation of neoplastic cells in chronic lymphocytic leukemia (CLL) after the short-term and long-term administration of ibrutinib. We aimed to assess the influence of short-term and long-term ibrutinib treatment on the HLA-DR expression on CLL cells, T cells and monocytes. The immunophenotyping of CLL and immune cells in peripheral blood was performed on 16 high-risk CLL patients treated with ibrutinib. After early ibrutinib administration, the HLA-DR expression on CLL cells reduced ( P = 0.032), accompanied by an increase in CLL cell counts in peripheral blood ( P = 0.001). In vitro culturing of CLL cells with ibrutinib also revealed the reduction in the HLA-DR expression at protein and mRNA levels ( P < 0.01). The decrease in HLA-DR on CLL cells after the first month was followed by the gradual increase of its expression by the 12th month ( P = 0.001). A one-month follow-up resulted in elevated absolute counts of CD4 + ( P = 0.002) and CD8 + ( P < 0.001) T cells as well as CD4 + and CD8 + cells bearing HLA-DR ( P < 0.01). The long-term administration of ibrutinib was associated with the increased numbers of CD4 + bearing HLA-DR ( P = 0.006) and elevation of HLA-DR expression on all monocyte subsets ( P ≤ 0.004). Our results provide the first evidence of the time-dependent immunomodulatory effect of ibrutinib on CLL and T cells and monocytes. The clinical consequences of time-dependent changes in HLA-DR expression in ibrutinib treated patients deserve further investigation.