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The clinical efficacy of BTK inhibitors in the treatment of CLL

Studies of BTK as a target have enjoyed substantial popularity among the researcher circle ever since its role in B-cell maturation as well as in mast cell activation through the high-affinity IgE receptor have been confirmed, which given rise to the development of a diverse array of BTK inhibitors.

†Ibrutinib and Acalabrutinib are two BTK inhibitors that have already been approved for clinical use, while there are many other BTK inhibitors with published structures, such as Olmutinib, Tirabrutinib, Spebrutinib and more.

Recently, AstraZeneca, a global science-led biopharmaceutical company, announces that the company's BTK inhibitor drug Calquence (acalabrutinib) for the treatment of stage 3 clinically in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) has reached the endpoints, and statistically significantly improved progression-free survival (PFS) has been achieved compared with the active control group. According to Dr. Josť Baselga, executive vice president of oncology research and development at the company, Calquence is the first BTK inhibitor in a phase 3 clinical trial to be superior to existing standard combinational therapies in the treatment of patients with relapsed/refractory CLL.

CLL is the most common type of leukemia in adults. In the United States, it accounts for a quarter of the total number of new leukemia patients. Excessive hematopoietic stem cells in the bone marrow of CLL patients produce abnormal lymphocytes, and these abnormal cells do not normally fight infection. An increase in the number of abnormal cells simultaneously reduces the production of normal white blood cells, red blood cells, and platelets. This can lead to anemia, infection and bleeding.

The BTK-mediated B cell receptor signaling pathway is an important signaling pathway for stimulating CLL growth. Calquence can inhibit BTK activity by covalent binding to BTK. The new drug has been approved by the FDA in 2017 for the treatment of adult patients with mantle cell carcinoma (MCL) who have received a pre-treatment.

In a global, multicenter, randomized, open-label, phase 3 trial called ASCEND, 310 CLL patients who had undergone pre-treatment were divided into two groups, each receiving Calquence monotherapy, or a combination therapy of rituximab plus idlelisib or bendamustine. The primary endpoint of the trial was the PFS assessed by the Independent Review Board (IRC). The results of the trial showed that Calquence as a monotherapy resulted in a statistically significant and clinically significant improvement in PFS in patients compared to the control group.

The relevant details of the research results will be published at future medical conferences. At the same time, Calquence is also used as a first-line therapy in a phase 3 clinical trial called ELEVATE-TN to treat patients with newly diagnosed CLL. Obviously, this new drug may be a new treatment option for CLL patients.

BOC Sciences provides BTK inhibitors and many other therapeutic inhibitors such as GPR119 Inhibitor, CD39 InhibitorFree Articles, ICOS Inhibitor and CD27 Inhibitor for research scientists.

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The author has been writing articles for 6 years in the area of biochemistry,biology and science.

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