keyword
MENU ▼
Read by QxMD icon Read
search

Venetoclax cll

keyword
https://www.readbyqxmd.com/read/28100580/venetoclax-in-patients-with-previously-treated-chronic-lymphocytic-leukemia
#1
Andrew W Roberts, Stephan Stilgenbauer, John F Seymour, David C S Huang
Venetoclax is the first BCL2 inhibitor to enter routine clinical practice. It is an orally bioavailable small molecule that binds BCL2 very specifically. Acting as a pharmacological mimic of the proteins that initiate apoptosis (a so-called BH3-mimetic), venetoclax rapidly induces apoptosis in chronic lymphocytic leukemia (CLL) cells which express high levels of BCL2 and rely on it to maintain their survival. As a single agent, daily venetoclax treatment induced durable responses in 79% of patients with relapsed or refractory CLL or small lymphocytic lymphoma in a Phase 1 study, including complete remissions in 20% of patients...
January 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28095146/phase-i-first-in-human-study-of-venetoclax-in-patients-with-relapsed-or-refractory-non-hodgkin-lymphoma
#2
Matthew S Davids, Andrew W Roberts, John F Seymour, John M Pagel, Brad S Kahl, William G Wierda, Soham Puvvada, Thomas J Kipps, Mary Ann Anderson, Ahmed Hamed Salem, Martin Dunbar, Ming Zhu, Franklin Peale, Jeremy A Ross, Lori Gressick, Monali Desai, Su Young Kim, Maria Verdugo, Rod A Humerickhouse, Gary B Gordon, John F Gerecitano
Purpose B-cell leukemia/lymphoma-2 (BCL-2) overexpression is common in many non-Hodgkin lymphoma (NHL) subtypes. A phase I trial in patients with NHL was conducted to determine safety, pharmacokinetics, and efficacy of venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor. Patients and Methods A total of 106 patients with relapsed or refractory NHL received venetoclax once daily until progressive disease or unacceptable toxicity at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts...
January 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28089635/venetoclax-plus-rituximab-in-relapsed-or-refractory-chronic-lymphocytic-leukaemia-a-phase-1b-study
#3
John F Seymour, Shuo Ma, Danielle M Brander, Michael Y Choi, Jacqueline Barrientos, Matthew S Davids, Mary Ann Anderson, Anne W Beaven, Steven T Rosen, Constantine S Tam, Betty Prine, Suresh K Agarwal, Wijith Munasinghe, Ming Zhu, L Leanne Lash, Monali Desai, Elisa Cerri, Maria Verdugo, Su Young Kim, Rod A Humerickhouse, Gary B Gordon, Thomas J Kipps, Andrew W Roberts
BACKGROUND: Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. METHODS: Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial...
January 12, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28081486/front-line-treatment-of-cll-in-the-era-of-novel-agents
#4
REVIEW
Tadeusz Robak, Stephan Stilgenbauer, Alessandra Tedeschi
Although chemoimmunotherapy prolongs survival and as such, is the standard of care for treatment-naïve patients, its effectiveness may be reduced by associated toxicity and dose reductions. In addition, it has been associated with the development of myelosuppression and secondary neoplasms; treatments are hence needed which offer greater survival and lowered toxicity. A range of new targeted agents, ibrutinib, idelalisib and venetoclax, have demonstrated such a balance in a second-line setting, offering CLL patients durable remissions and a modest toxicity profile...
December 30, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28056525/venetoclax
#5
Amber C King, Tim J Peterson, Troy Z Horvat, Mabel Rodriguez, Laura A Tang
OBJECTIVE: To review the pharmacology, efficacy, and safety of venetoclax for treatment of lymphoid malignancies. DATA SOURCES: A literature search was performed of PubMed and MEDLINE databases (2005 to September 2016), abstracts from the American Society of Hematology and the American Society of Clinical Oncology, and ongoing studies from clinicaltrials.gov. Searches were performed utilizing the following key terms: venetoclax, ABT-199, GDC-199, obatoclax, GX15-070, BCL-2 inhibitor, navitoclax, ABT-263, and Venclexta...
December 1, 2016: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28052338/quantitative-prediction-of-the-effect-of-cyp3a-inhibitors-and-inducers-on-venetoclax-pharmacokinetics-using-a-physiologically-based-pharmacokinetic-model
#6
Kevin J Freise, Mohamad Shebley, Ahmed Hamed Salem
The objectives of the analysis were to develop and verify a venetoclax physiologically based pharmacokinetic (PBPK) model to predict the effects of cytochrome P450 3A (CYP3A) inhibitors and inducers on the PK of venetoclax and inform dosing recommendations. A minimal PBPK model was developed based on prior in vitro and in vivo clinical data using a "middle-out" approach. The PBPK model was independently verified against clinical studies of the strong CYP3A inhibitor ketoconazole, the strong CYP3A inducer, multiple-dose rifampin, and the steady-state venetoclax PK in chronic lymphocytic leukemia (CLL) subjects by comparing predicted to observed ratios of the venetoclax maximum concentration (Cmax R) and area under the curve from time 0 to infinity (AUC∞ R) from these studies...
January 4, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28017967/duvelisib-treatment-is-associated-with-altered-expression-of-apoptotic-regulators-that-helps-in-sensitization-of-chronic-lymphocytic-leukemia-cells-to-venetoclax-abt-199
#7
V M Patel, K Balakrishnan, M Douglas, T Tibbitts, E Y Xu, J L Kutok, M Ayers, A Sarkar, R Guerrieri, W G Wierda, S O'Brien, N Jain, H M Stern, V Gandhi
Duvelisib, an oral dual inhibitor of PI3K-δ and PI3K-γ, is in phase III trials for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin's lymphoma (iNHL). In CLL, duvelisib monotherapy is associated with high iwCLL and nodal response rates, but complete remissions are rare. To characterize the molecular effect of duvelisib, we obtained samples from CLL patients on the duvelisib phase I trial. Gene-expression studies (RNA seq, Nanostring, Affymetrix array, and real time RT-PCR) demonstrated increased expression of BCL2 along with several BH3-only pro-apoptotic genes...
December 26, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27993930/absorption-metabolism-and-excretion-of-a-novel-bcl-2-inhibitor-venetoclax-in-humans
#8
Hong Liu, Melissa J Michmerhuizen, Yanbin Lao, Katty Wan, Ahmed Hamed Salem, James Sawicki, Michael Serby, Srirajan Vaidyanathan, Shekman L Wong, Suresh Agarwal, Martin Dunbar, Jens Sydor, Sonia Maria de Morais, Anthony J Lee
Venetoclax (also known as ABT-199) is a B-cell lymphoma-2 (Bcl-2) family protein inhibitor and is currently in clinical development for the treatment of chronic lymphocytic leukaemia (CLL) and other hematological malignancies. The objective of this study was to characterize the absorption, metabolism, and excretion of venetoclax in humans. Following a single oral dose of 200 mg (100 μ - Ci) of [(14)C]venetoclax to four healthy volunteers, recovery of total radioactive dose was 100% (± 5%), with feces being the major route of elimination of the administered dose, whereas urinary excretion was minimal (<0...
December 19, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27990281/mitochondrial-apoptosis-and-bh3-mimetics
#9
REVIEW
Haiming Dai, X Wei Meng, Scott H Kaufmann
The BCL2-selective BH3 mimetic venetoclax was recently approved for the treatment of relapsed, chromosome 17p-deleted chronic lymphocytic leukemia (CLL) and is undergoing extensive testing, alone and in combination, in lymphomas, acute leukemias, and solid tumors. Here we summarize recent advances in understanding of the biology of BCL2 family members that shed light on the action of BH3 mimetics, review preclinical and clinical studies leading to the regulatory approval of venetoclax, and discuss future investigation of this new class of antineoplastic agent...
2016: F1000Research
https://www.readbyqxmd.com/read/27982454/relationship-between-venetoclax-exposure-rituximab-coadministration-and-progression-free-survival-in-patients-with-relapsed-or-refractory-chronic-lymphocytic-leukemia-demonstration-of-synergy
#10
Kevin J Freise, Aksana K Jones, Rajeev M Menon, Maria E Verdugo, Rod A Humerickhouse, Walid M Awni, Ahmed Hamed Salem
Venetoclax is indicated at a dosage of 400 mg daily (QD) for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion who have received at least 1 prior therapy. Ongoing trials are evaluating venetoclax in combination with CD20 targeting monoclonal antibodies, such as rituximab. The objective of this research was to characterize the relationship between venetoclax exposures and progression-free survival (PFS) and to evaluate the effect of rituximab coadministration on PFS in patients with relapsed or refractory (R/R) CLL/small lymphocytic lymphoma (SLL)...
December 16, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27913471/sequencing-of-chronic-lymphocytic-leukemia-therapies
#11
Jacqueline C Barrientos
It is an unprecedented time for the treatment of patients with chronic lymphocytic leukemia (CLL) with the recent approval of several targeted agents for use in frontline, relapsed, refractory, and high-risk disease. Traditionally, frontline management of CLL has been a combination of chemotherapy (fludarabine, cyclophosphamide, bendamustine, or chlorambucil) with an anti-CD20 monoclonal antibody (rituximab, ofatumumab, obinutuzumab). The current landscape is rapidly evolving with the advent of therapies that demonstrate selective inhibition of important pathways necessary for CLL proliferation and survival...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27889784/targeted-therapy-of-cll
#12
Othman Al-Sawaf, Kirsten Fischer, Barbara Eichhorst, Michael Hallek
The landscape of chronic lymphocytic leukemia (CLL) has undergone profound changes in the past years. First, the addition of CD20-targeting antibodies to conventional chemotherapy has improved the therapeutic outcome in the majority of CLL patients. Since the establishment of the critical role of the B cell receptor signaling pathway in the pathogenesis of CLL, several agents have been developed to target this pathway. Ibrutinib and idelalisib, 2 potent kinase inhibitors, have both become available for CLL therapy in the first and second line...
2016: Oncology Research and Treatment
https://www.readbyqxmd.com/read/27859472/effect-of-ketoconazole-a-strong-cyp3a-inhibitor-on-the-pharmacokinetics-of-venetoclax-a-bcl-2-inhibitor-in-patients-with-non-hodgkin-lymphoma
#13
Suresh K Agarwal, Ahmed Hamed Salem, Alexey V Danilov, Beibei Hu, Soham Puvvada, Martin Gutierrez, David Chien, Lionel D Lewis, Shekman L Wong
AIMS: To examine the effect of a strong cytochrome P450 (CYP) 3A inhibitor, ketoconazole, on the pharmacokinetics, safety and tolerability of venetoclax. METHODS: Twelve patients with non-Hodgkin lymphoma (NHL) were enrolled in this Phase 1, open-label, fixed-sequence study. Patients received a single 50 mg dose of venetoclax orally on Day 1 and Day 8, and a 400 mg once daily dose of ketoconazole on Days 5-11. Blood samples were collected predose and up to 96 h after each venetoclax dose on Day 1 and Day 8...
November 2, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27854102/the-next-generation-of-targeted-molecules-for-the-treatment-of-chronic-lymphocytic-leukemia
#14
REVIEW
Deepa Jeyakumar, Susan O'Brien
With the recent approval of several new targeted therapies for chronic lymphocytic leukemia (CLL), there are now multiple options for its treatment. Inhibitors of Bruton tyrosine kinase (with ibrutinib being the first-in-class US Food and Drug Administration-approved agent) and phosphoinositide 3-kinase (with idelalisib as the first-in-class approved agent) are promising because they are generally well tolerated and highly effective against this malignancy. These agents may be particularly important in the treatment of older patients who are less able to tolerate the myelosuppression (and subsequent infections) associated with chemoimmunotherapy...
November 15, 2016: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/27808579/predictive-and-prognostic-biomarkers-in-the-era-of-new-targeted-therapies-for-chronic-lymphocytic-leukemia
#15
Davide Rossi, Bernhard Gerber, Georg Stüssi
Treatment options for chronic lymphocytic leukemia (CLL) have improved with the introduction of the B-cell receptor inhibitors ibrutinib and idelalisib, and of the BCL2 inhibitor venetoclax. While awaiting the results of head to head comparisons between novel agents and chemoimmunotherapy, predictive biomarkers can assist physicians in treatment tailoring. Though novel agents have modified the landscape of predictors at the time of treatment requirement, the usefulness of historical CLL prognostic biomarkers is still up-to-date when considering anticipation of time to first treatment...
November 3, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27806433/targeting-bcl2-with-bh3-mimetics-basic-science-and-clinical-application-of-venetoclax-in-chronic-lymphocytic-leukemia-and-related-b-cell-malignancies
#16
A W Roberts, Dcs Huang
The intracellular protein B-cell-lymphoma-2 (BCL2) has been considered an attractive target for cancer therapy since the discovery of its function as a major promoter of cell survival (an anti-apoptotic) in the late 1980s. However, the challenges of targeting a protein-protein interaction delayed the discovery of fit-for-purpose molecules until the mid-2000s. Since then, a series of high affinity small organic molecules that inhibits the interaction of BCL2 with the apoptotic machinery, the so-called BH3-mimetics, have been developed...
January 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27796157/management-of-elderly-and-unfit-patients-with-chronic-lymphocytic-leukemia
#17
Francesca R Mauro, Adriano Salaroli, Maria D Caputo, Gioia Colafigli, Luigi Petrucci, Melissa Campanelli, Antonietta Ferretti, Anna R Guarini, Robin Foà
About 75% of patients with chronic lymphocytic leukemia (CLL) are more than 65 years at the time of diagnosis. Treatment of the elderly remains complicated due to multiple factors, such as comorbidities, decline in functional reserve and fitness. Since chronological age by itself cannot properly predict life expectancy and treatment tolerance, an accurate assessment of the fitness status is of crucial importance for an optimal treatment choice. Areas covered: This review will discuss the most relevant aspects concerning the issues experienced in the management of elderly/unfit patients with CLL...
December 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27742072/current-state-of-hematopoietic-cell-transplantation-in-cll-as-smart-therapies-emerge
#18
Mohamed A Kharfan-Dabaja, Jessica El-Asmar, Farrukh T Awan, Mehdi Hamadani, Ernesto Ayala
Novel therapies targeting various kinases downstream of the B-cell receptor have emerged along with monoclonal antibodies and BCL-2 antagonists, and are changing the therapeutic landscape of chronic lymphocytic leukemia. However, cure remains unattainable unless eligible patients are offered an allogeneic hematopoietic cell transplant. Access to allogeneic hematopoietic cell transplantation has expanded considerably with availability of reduced intensity conditioning regimens which is capable offering durable remissions even in poor-risk disease...
March 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27742065/current-strategies-to-create-tailored-and-risk-adapted-therapies-for-cll-patients
#19
Paula Cramer, Barbara Eichhorst, Hans Christian Reinhardt, Michael Hallek
Given the current dynamics in the development of novel agents for CLL therapy, the task to find optimal, non-toxic combinations has become the primary goal. This article gives an update of the most interesting novel drugs. The strategy of the German CLL Study Group to use these agents in combinations is described in detail, highlighting the strategy and first results of a recently started series of phase II combination trials, the BXX series using agents such as bendamustine, idelalisib, ibrutinib, obinutuzumab, ofatumumab and venetoclax...
March 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27697994/the-dual-syk-jak-inhibitor-cerdulatinib-antagonises-b-cell-receptor-and-microenvironmental-signaling-in-chronic-lymphocytic-leukemia
#20
Matthew D Blunt, Stefan Koehrer, Rachel Dobson, Marta Larrayoz, Sarah Wilmore, Alice Hayman, Jack Parnell, Lindsay D Smith, Andrew Davies, Peter Wm Johnson, Pamela B Conley, Anjali Pandey, Jonathan C Strefford, Freda K Stevenson, Graham Packham, Francesco Forconi, Greg P Coffey, Jan Burger, Andrew J Steele
PURPOSE: B-cell receptor (BCR)-associated kinase inhibitors such as ibrutinib have revolutionised the treatment of chronic lymphocytic leukemia (CLL). However, these agents are not curative and resistance is already emerging in a proportion of patients. Interleukin-4 (IL-4), expressed in CLL lymph nodes, can augment BCR-signalling and reduce the effectiveness of BCR-kinase inhibitors. Therefore simultaneous targeting of the IL-4- and BCR-signalling pathways by cerdulatinib, a novel dual Syk/JAK inhibitor currently in clinical trials (NCT01994382), may improve treatment responses in patients...
October 3, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
keyword
keyword
91726
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"