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Ibrutinib

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https://www.readbyqxmd.com/read/28526963/incorporation-of-the-time-varying-postprandial-increase-in-splanchnic-blood-flow-into-a-pbpk-model-to-predict-the-effect-of-food-on-the-pharmacokinetics-of-orally-administered-high-extraction-drugs
#1
Rachel H Rose, David B Turner, Sibylle Neuhoff, Masoud Jamei
Following a meal, a transient increase in splanchnic blood flow occurs that can result in increased exposure to orally administered high-extraction drugs. Typically, physiologically based pharmacokinetic (PBPK) models have incorporated this increase in blood flow as a time-invariant fed/fasted ratio, but this approach is unable to explain the extent of increased drug exposure. A model for the time-varying increase in splanchnic blood flow following a moderate- to high-calorie meal (TV-Q Splanch) was developed to describe the observed data for healthy individuals...
May 19, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28526063/targeting-the-cxcr4-pathway-using-a-novel-anti-cxcr4-igg1-antibody-pf-06747143-in-chronic-lymphocytic-leukemia
#2
Manoj K Kashyap, Carlos I Amaya-Chanaga, Deepak Kumar, Brett Simmons, Nanni Huser, Yin Gu, Max Hallin, Kevin Lindquist, Rolla Yafawi, Michael Y Choi, Ale-Ali Amine, Laura Z Rassenti, Cathy Zhang, Shu-Hui Liu, Tod Smeal, Valeria R Fantin, Thomas J Kipps, Flavia Pernasetti, Januario E Castro
BACKGROUND: The CXCR4-CXCL12 axis plays an important role in the chronic lymphocytic leukemia (CLL)-microenvironment interaction. Overexpression of CXCR4 has been reported in different hematological malignancies including CLL. Binding of the pro-survival chemokine CXCL12 with its cognate receptor CXCR4 induces cell migration. CXCL12/CXCR4 signaling axis promotes cell survival and proliferation and may contribute to the tropism of leukemia cells towards lymphoid tissues and bone marrow...
May 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28504030/practical-recommendations-for-the-choice-of-anticoagulants-in-the-management-of-patients-with-atrial-fibrillation-on-ibrutinib
#3
Khai Li Chai, Gail Rowan, John F Seymour, Kate Burbury, Dennis Carney, Constantine S Tam
The management of AF represents a major challenge in patients with CLL, especially in elderly patients with multiple comorbidities who are representative of the majority of patients with CLL. This is especially complex in the case of ibrutinib. Many anticoagulants have potential for pharmacological interaction with ibrutinib, and ibrutinib itself has antiplatelet properties. Use of ibrutinib therapy in these patients mandates review and revision of the need for anticoagulation and best anticoagulant to use...
May 15, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28503927/infectious-complications-in-chronic-lymphocytic-leukemia-a-retrospective-analysis-single-institution-experience
#4
L Demitrovicova, E Mikuskova, I Oravcova, S Cingelova, L Drgona, B Mladosievicova
The aim of this study was to evaluate the incidence of a variety of infectious complications in patients with CLL regarding the duration of CLL and the type of treatment. We present the retrospective analysis of patients with CLL treated at our institution in years 2004-2016. We collected data about the type of infection, pathogenes, treatment and severity of infections surpassed in connection with administration treatment. In the study one hundred and ten patients were evaluated. The average age of patients was 61...
2017: Neoplasma
https://www.readbyqxmd.com/read/28503240/response-of-renal-cell-carcinoma-to-ibrutinib-a-bruton-tyrosine-kinase-inhibitor-in-a-patient-treated-for-chronic-lymphocytic-leukemia
#5
Gregory W Hosier, Naji J Touma
No abstract text is available yet for this article.
May 2017: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28495793/usp7-inhibition-alters-homologous-recombination-repair-and-targets-cll-cells-independent-of-atm-p53-functional-status
#6
Angelo Agathanggelou, Edward Smith, Nicholas J Davies, Marwan Kwok, Anastasia Zlatanou, Ceri E Oldreive, Jingwen Mao, David Da Costa, Sina Yadollahi, Tracey Perry, Pamela Kearns, Anna Skowronska, Elliot Yates, Helen Parry, Peter Hillmen, Celine Reverdy, Remi Delansorne, Shankara Paneesha, Guy Pratt, Paul Moss, A Malcolm R Taylor, Grant S Stewart, Tatjana Stankovic
The role of the deubiquitylase ubiquitin-specific protease 7 (USP7) in the regulation of the p53-dependent DNA damage response (DDR) pathway is well established. Whilst previous studies have mostly focused on the mechanisms underlying how USP7 directly controls p53 stability, we have recently shown that USP7 modulates the stability of the DNA damage responsive E3 ubiquitin ligase, RAD18. This suggests that targeting USP7 may have therapeutic potential even in tumors with defective p53 or ibrutinib resistance...
May 11, 2017: Blood
https://www.readbyqxmd.com/read/28482721/the-potential-combination-of-bcl-2-inhibitors-and-ibrutinib-as-frontline-therapy-in-chronic-lymphocytic-leukemia
#7
Andrew Aw, Jennifer R Brown
The recent development of small molecule inhibitors targeted at the B-cell receptor (BCR) pathway and the anti-apoptotic protein BCL-2 has revolutionized the care of patients with chronic lymphocytic leukemia (CLL). While durable responses to the BCR inhibitor ibrutinib have been observed in both previously untreated and relapsed/refractory CLL patients, residual disease is common in patients treated with single-agent ibrutinib. Interest remains high in therapeutic combinations that may lead to better quality remissions...
May 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28480764/novel-agents-in-mantle-cell-lymphoma
#8
David Tucker, Simon Rule
Mantle cell lymphoma (MCL) usually takes an aggressive clinical course and carries a poor prognosis. Recently, progress has been made in the treatment of MCL including the development of a number of novel agents which target intracellular pathways and the extracellular microenvironment. These agents have transformed the landscape of available therapeutic options. Areas covered: The current literature on the novel agents which currently hold a licence for the treatment of MCL in the context of front-line therapy and in the relapsed/refractory setting is summarized...
May 17, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28480254/disseminated-cryptococcosis-with-brain-involvement-in-patients-with-chronic-lymphoid-malignancies-on-ibrutinib
#9
Julia A Messina, Eileen K Maziarz, Andrej Spec, Dimitrios P Kontoyiannis, John R Perfect
We report 2 cases of disseminated cryptococcosis with central nervous system involvement in patients with chronic lymphoid malignancies occurring within 1 month of starting on ibrutinib. Characteristically, in both cases, no inflammation was seen in the cerebrospinal fluid. Central nervous system mycoses should be considered as a potential complication of ibrutinib.
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28471569/concomitant-treatment-with-ibrutinib-and-amiodarone-causing-reversible-heart-failure-syndrome
#10
Yishay Wasserstrum, Pia Raanani, Ran Kornowski, Zaza Iakobishvili
No abstract text is available yet for this article.
July 2016: Israel Medical Association Journal: IMAJ
https://www.readbyqxmd.com/read/28470742/platelet-proteins-cause-basophil-histamine-release-through-an-immunoglobulin-dependent-mechanism
#11
Donna Dong-Young Lee, Igla Muskaj, William Savage
BACKGROUND: A general understanding of allergic transfusion reaction mechanisms remains elusive. Multiple mechanisms have been proposed, but none have been compared experimentally. STUDY DESIGN AND METHODS: We used histamine release (HR) from healthy human donor basophils to model allergic transfusion reactions. Platelet component supernatant (plasma), platelet lysate, and manipulated platelet lysates (dialyzed, delipidated, trypsinized, mild heat-inactivated, and ultracentrifuged) were used to characterize allergic stimuli...
May 4, 2017: Transfusion
https://www.readbyqxmd.com/read/28469834/ibrutinib-associated-skin-toxicity-a-case-of-maculopapular-rash-in-a-79-year-old-caucasian-male-patient-with-relapsed-waldenstrom-s-macroglobulinemia-and-review-of-the-literature
#12
Anders Bisgaard Jensen, Birgitte Stausbøl-Grøn, Rikke Riber-Hansen, Francesco d'Amore
Waldenstrom's macroglobulinamia (WM) is a rare malignant lymphoproliferative disorder, characterized by monoclonal IgM paraproteinemia and neoplastic proliferation of malignant lymphoplasmacytoid cells in the bone marrow. Traditionally, WM has been treated with modalities similar to those used in the management of other indolent lymphomas. Just recently, based on impressive clinical trial results in heavily pretreated WM patients, a new Bruton Tyrosine Kinase-inhibitor, Ibrutinib, has been approved for the treatment of this disorder...
March 13, 2017: Dermatology Reports
https://www.readbyqxmd.com/read/28462919/targeting-antigen-independent-proliferation-in-chronic-lymphocytic-leukemia-through-differential-kinase-inhibition
#13
E Slinger, R Thijssen, A P Kater, E Eldering
The clinical success of B cell receptor (BCR) signaling pathway inhibitors in chronic lymphocytic leukemia (CLL) is attributed to inhibition of adhesion in and migration towards the lymph node. Proliferation of CLL cells is restricted to this protective niche, but the underlying mechanism(s) is/are not known. Treatment with BCR pathway inhibitors results in rapid reductions of total clone size, while CLL cell survival is not affected, which points towards inhibition of proliferation. However, BCR stimulation does not induce proliferation of CLL in vitro, while triggering via TLR-, TNF- or cytokine- receptors does...
May 2, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28460620/cx-4945-a-selective-inhibitor-of-casein-kinase-2-synergizes-with-b-cell-receptor-signaling-inhibitors-in-inducing-diffuse-large-b-cell-lymphoma-cell-death
#14
Elisa Mandato, Sara Canovas Nunes, Fortunato Zaffino, Alessandro Casellato, Paolo Macaccaro, Laura Quotti Tubi, Andrea Visentin, Livio Trentin, Gianpietro Semenzato, Francesco Piazza
BACKGROUND: Approximately one third of Diffuse Large B cell Lymphomas (DLBCL) are refractory or relapse. Novel therapeutic approaches under scrutiny include inhibitors of B-cell receptor (BCR) signaling. Protein kinase CK2 propels survival, proliferation and stress response in solid and hematologic malignancies and promotes a "non-oncogene addiction" phenotype. Whether this kinase regulates BCR signaling thus being a suitable pharmacological target in DLBCL is unknown. OBJECTIVE: To establish if CK2 controls DLBCL cell survival and the BCR signaling; to check if the combination of CK2 inhibitor CX-4945 and BCR blockers Ibrutinib and Fostamatinib is more effectively cytotoxic for DLBCL cells than the single agents; to survey the changes in signaling molecules downstream BCR upon CK2 inhibition...
April 26, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28459097/lower-extremity-ecchymotic-nodules-in-a-patient-being-treated-with-ibrutinib-for-chronic-lymphocytic-leukemia
#15
Josh A Hammel, Gretchen M Roth, Nkanyezi Ferguson, Janet A Fairley
No abstract text is available yet for this article.
May 2017: JAAD Case Reports
https://www.readbyqxmd.com/read/28453705/optimal-sequencing-of-ibrutinib-idelalisib-and-venetoclax-in-chronic-lymphocytic-leukemia-results-from-a-multicenter-study-of-683-patients
#16
A R Mato, B T Hill, N Lamanna, P M Barr, C S Ujjani, D M Brander, C Howlett, A P Skarbnik, B D Cheson, C S Zent, J J Pu, P Kiselev, K Foon, J Lenhart, S Henick Bachow, A M Winter, A-L Cruz, D F Claxton, A Goy, C Daniel, K Isaac, K H Kennard, C Timlin, M Fanning, L Gashonia, M Yacur, J Svoboda, S J Schuster, C Nabhan
Background: Ibrutinib, idelalisib, and venetoclax are approved for treating CLL patients in the United States. However, there is no guidance as to their optimal sequence. Patients and methods: We conducted a multicenter, retrospective analysis of CLL patients treated with kinase inhibitors (KIs) or venetoclax. We examined demographics, discontinuation reasons, overall response rates (ORR), survival, and post-KI salvage strategies. Primary endpoint was progression-free survival (PFS)...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28447276/increased-dabigatran-plasma-concentration-during-ibrutinib-treatment-a-case-of-cerebral-hemorrhage-and-successful-dabigatran-reversal-by-idarucizumab
#17
R Quintavalla, M Lombardi, P Prandoni, C Manotti, I Tadonio, F Re, P M Ferrini, M I Tassoni, P Rossetti, F Quaini
No abstract text is available yet for this article.
April 26, 2017: Aging Clinical and Experimental Research
https://www.readbyqxmd.com/read/28439761/small-molecule-inhibitors-in-chronic-lymphocytic-lymphoma-and-b-cell-non-hodgkin-lymphoma
#18
REVIEW
Allison Rosenthal
PURPOSE OF REVIEW: The purpose of this review is to summarize the available literature for the use of small molecule inhibitors in chronic lymphocytic leukemia and B cell non-Hodgkin lymphoma. RECENT FINDINGS: Ibrutinib, idelalisib, and venetoclax are small molecule inhibitors that have revolutionized therapeutic options for patients with CLL, particularly for those with high-risk disease including 17p deletion. These drugs are increasingly finding application in a variety of subtypes of B cell NHL...
April 24, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28428442/combination-of-ibrutinib-and-abt-199-in-diffuse-large-b-cell-lymphoma-and-follicular-lymphoma
#19
Hsu-Ping Kuo, Scott A Ezell, Karl J Schweighofer, Leo Wk Cheung, Sidney Hsieh, Mutiah Apatira, Mint Sirisawad, Karl Eckert, Ssucheng J Hsu, Chun-Te Chen, Darrin M Beaupre, Matthias Versele, Betty Y Chang
Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton's tyrosine kinase (BTK)-mediated B-cell receptor (BCR) signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28428233/efficacy-in-the-margins-of-nhl-with-ibrutinib
#20
Paul M Barr
No abstract text is available yet for this article.
April 20, 2017: Blood
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