Bruton Tyrosine Kinase (BTK) and Its Role in B-cell Malignancy

Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study

“…6 Ibrutinib binds to a cysteine residue (Cys481) in the active site of the ATP-binding domain of Bruton's tyrosine kinase, which then inhibits B-cell receptor signalling within the malignant B cell with downstream mitigation of cell growth, proliferation, survival, adhesion, and migration. [7][8][9][10][11][12] Effi cacy results from previous studies have shown signifi cant single-agent activity of ibrutinib in the treatment of relapsed or refractory mantle-cell lymphoma. A single-arm phase 1b/2 study of ibrutinib in which patients with relapsed or refractory mantle-cell lymphoma were stratifi ed by previous bortezomib exposure had an investigator-assessed overall response rate of 68%, with a complete response rate of 21%, and a median duration of response of 17•5 months.…”

“…See Online for appendix randomly permuted blocks and stratifi ed by number of previous lines of therapy (one, two, or three or more) and simplifi ed mantle-cell lymphoma international prognostic index (sMIPI) score 22 (low risk [0-3] vs intermediate risk [4][5] vs high risk [6][7][8][9][10][11]). The randomisation scheme was implemented within the interactive web response system that determined treatment assignment and matching study drug kits.…”

Safety and activity of BTK inhibitor ibrutinib combined with ofatumumab in chronic lymphocytic leukemia: a phase 1b/2 study

“…Ibrutinib was administered orally at a dose of 420 mg once daily and continued until disease progression or unacceptable toxicity. Ofatumumab was administered intravenously per prescribing information (300 mg for dose 1/2000 mg for doses [2][3][4][5][6][7][8][9][10][11][12]. Patients could then continue daily ibrutinib in extension study PCYC-1103-CA until progression or intolerability.…”

“…Proximal within this pathway, Bruton tyrosine kinase (BTK), a member of the Tec kinase family, plays a central role in activation of downstream signaling required for survival and proliferation of malignant B cells. [11][12][13][14][15] BTK is also critical for B-cell development and function in relation to the homing, migration, and adhesion of B cells to bone marrow or lymphoid tissues. 16,17 Ibrutinib is a first-in-class, orally administered, once-daily covalent inhibitor of BTK.…”

PRIMA1 ile lösemi hücrelerinde Bruton tirozin kinaz inhibisyonu aracılığı apoptoz uyarımı

“…Btk up-regulation has been reported in many B cell leukemias and lymphomas, which is shown to be important regulator for the tissue homing, adhesion and migration of tumor cells [18][19][20][21][22] . Therefore, targeting Btk for treating various B cell malignancies using inhibitors has been intensively studied.…”