Studies have shown that CLL patients receiving imatinib treatment according to Lu normal B cells and humoral immunity occurred partially reconstructed

Recently, an analysis of Sun and his colleagues on the "Blood" published in the journal, according to Lu imatinib in chronic lymphocytic leukemia (CLL) patients - after Bruton tyrosine kinase (BTK) inhibitor therapy, normal B cells and humoral immunity occurred partially reconstructed.
BTK plays an essential role in B cell antigen receptor signaling pathway, and is involved in cytokine-mediated signaling pathway in macrophages. In recent years, BTK inhibitors have been used in the treatment of malignant B cell tumors, and mantle cell lymphoma. Relevant literature, according to Lu imatinib - A US Food and Drug Administration (FDA) approved the oral BTK inhibitor, for treatment of refractory / relapsed CLL or untreated CLL, excellent efficacy.
However, it is worth noting that, BTK inhibitors antitumor activity not only depend on the interrupt BCR signaling, adhesion and migration but also targeting Toll-like receptor signaling and B cells. According to Lu CLL patients receiving imatinib after treatment overall response rate was 90%. Since CLL is low agammaglobulinemia and immune disorders characterized by repeated infections cause, so the effect of this combination is very interesting. Given the BTK essential for B cell function is, therefore, according to Lu CLL efficacy of imatinib therapy, need to immunoglobulin levels and the risk of infection is characterized. On the contrary, according to Lu after imatinib treatment, CLL and normal B cell differential sensitivity of BTK inhibitors may promote immune reconstitution.
In order to better define the prognosis of these two aspects, Sun, etc. to give a 86 untreated or refractory / relapsed CLL patients according to Lu imatinib therapy, and for at least 12 months after the patient's humoral and normal B cells to assess the situation. They found that decrease serum IgG levels after 6 months of treatment, as of 24 months was significantly lower (down to 23% of normal). Non-clonal serum IgM levels rapid improvement in six months, while in the 24 months after the time remains the same; the same, clonality serum IgM water 6 months and 24 months on average lower. In addition, during the treatment, 82% of patients with serum IgA levels continue to rise.
It is worth noting that the average decrease of a majority of patients with normal baseline IgG or IgM water, and IgA levels remained unchanged. More importantly, these results with previous findings indicate that most patients receiving imatinib after treatment according to Lu, serum IgG and IgM levels were reduced, while IgA levels are unchanged.
Researchers by analyzing the level of free light chains (FLCs) CLL patients found by the patient according to Lu imatinib therapy showed a normalized κ / λ ratio, rather than clonal FLCs remain stable or slightly elevated, suggesting these are Reconstruction of normal B cells.
Followed by flow cytometry analysis showed that B cells to rebuild normal immunoglobulin levels, the overall level of normal B cells and B cell subsets species, it is very important. Overall, after 12 months of treatment, although normal B cell counts in most patients still unusually low, but 78% of the treatment of young patients and 29% of relapsed / refractory CLL patients had normal B cells, and the presence of the cell cycle. Interestingly, the analysis showed that four patients recovery of normal B cells is still different from the normal population, which shows that at this time the B cell recovery was only partial.
So, these immunological changes impact on infection risk?
Sun and his colleagues found that in the first six-month period of treatment, relapsed / refractory CLL patients with infection rates greater. However, it is evident that the increase in serum IgA levels ≥50% of patients with low infection rates. Meanwhile, pneumonia is one of the long-term adverse effects according to Lu CLL patients after imatinib treatment.
According to Lu imatinib treatment CLL, patients can produce partial reconstruction of humoral and normal B cells and lower infection rates. However, the key problem remains, such as the ability to confirm the clinical results according to Lu erlotinib control CLL higher therapeutic activity, rather than a direct effect of the immune system? In addition, Sun's analysis immunodeficiency CLL not mentioned not only by the humoral immune damage caused, but also caused by normal T cells and natural killer cells dysregulation.
Therefore, a lot of research still needs to fully understand the impact of imatinib according to Lu on the entire immune system. Perhaps, targeting BCR interrupt direct effect does not explain this incomplete immune reconstitution. Therefore, the role of BTK inhibitors on other signaling pathways can affect immune reconstitution, but also need follow-up research to explore. At present, yet according to Lu serum IgA levels after imatinib treatment significantly increased the exact mechanism clear; BTK immune system is not clear and specific role of the so-called normal B cells whether emerging. Conversely, CLL patients after chemotherapy, all serum immunoglobulin were reduced; and after lenalidomide therapy, all serum immunoglobulin increased.
According to Lu imatinib is the first to be approved by the BCR pathway targeting drugs, and is a major breakthrough in the history of CLL treatment. Because according to Lu imatinib is administered continuously, it requires long-term follow-up to accurately assess the role of the drug on the immune system.