Acalabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, is associated with high overall response rates and durable remission in previously treated chronic lymphocytic leukemia (CLL); however, complete remissions were limited.
The development of bruton tyrosine kinase inhibitors (BTKi) has been a significant advancement in the treatment of chronic lymphocytic leukemia and related B-cell malignancies.
The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib is inducing durable responses in chronic lymphocytic leukemia (CLL) patients with refractory/relapsed disease or with TP53 defect, with BTK and phospholipase C gamma 2 (PLCG2) mutations representing the predominant mechanisms conferring secondary ibrutinib resistance.
Chronic activation of the Bruton's tyrosine kinase (BTK)-mediated B-cell receptor (BCR) signaling is a hallmark of many B-cell lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL).
Ibrutinib (PCI-32765) is the most advanced BTK inhibitor in clinical testing, with ongoing phase III clinical trials in patients with chronic lymphocytic leukemia and mantle-cell lymphoma.
Although rituximab-based immunochemotherapy remains the standard of treatment for chronic lymphocytic leukemia (CLL), the importance of Bruton's tyrosine kinase inhibitors such as ibrutinib is steadily increasing.
Ibrutinib, a Bruton's tyrosine kinase inhibitor has reformed the treatment of various B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia.
A head-to-head comparison of ibrutinib and acalabrutinib in CLL cell cultures and healthy T cells is needed to understand preclinical biologic and molecular effects.<b>Experimental Design:</b> Using samples from patients with CLL, we compared the effects of both BTK inhibitors on biologic activity, chemokine production, cell migration, BTK phosphorylation, and downstream signaling in primary CLL lymphocytes and on normal T-cell signaling to determine the effects on other kinases.<b>Results:</b> Both BTK inhibitors induced modest cell death accompanied by cleavage of PARP and caspase-3.
As just reported by previous report, Richter syndrome developing after ibrutinib therapy lacked resistance mutations of the BTK and PLCG2 genes, which are clonally related to the pre-existent CLL phase representing transformation from CLL.
Areas covered: Unique properties of both CLL and ibrutinib that complicate attempts to definitively conclude whether BTK/PLCG2 mutations are passengers or drivers of ibrutinib-resistant disease are reviewed.
Ibrutinib, a clinically approved irreversible BTK kinase inhibitor for Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia (CLL) etc, has been reported to be potent against EGFR mutant kinase and currently being evaluated in clinic for Non Small Cell Lung Cancer (NSCLC).
The Bruton's tyrosine kinase inhibitor ibrutinib is a highly effective, new targeted therapy for chronic lymphocytic leukemia (CLL) that thwarts leukemia cell survival, growth, and tissue homing.
The results showed that compound <b>11g</b> displayed the best inhibitory activity on BTK with an inhibition rate of 82.76% at 100 nM and excellent anti-proliferation activity on three B-cell leukemia lines (IC<sub>50</sub> = 3.66 μM, 6.98 μM, and 5.39 μM against HL60, Raji and Ramos, respectively).
These 4 agents include the Bruton tyrosine kinase inhibitor ibrutinib, the B-cell leukemia/lymphoma-2 inhibitor venetoclax, and the phosphatidylinositol-3 kinase inhibitors idelalisib and duvelisib.
Ibrutinib, an oral inhibitor of the Bruton's tyrosine kinase (BTK) has proved to be remarkably efficient against treatment naïve (TN), heavily pre-treated and high-risk chronic lymphocytic leukaemia (CLL), with limited adverse events.
We investigated a next-generation phosphoinositide-3-kinase-δ inhibitor (PI3K-δi), umbralisib, plus a Bruton tyrosine kinase inhibitor (BTKi), ibrutinib, in relapsed or refractory chronic lymphocytic leukaemia and mantle cell lymphoma.