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Obinutuzumab

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https://www.readbyqxmd.com/read/29750146/sensitive-detection-of-the-natural-killer-cell-mediated-cytotoxicity-of-anti-cd20-antibodies-and-its-impairment-by-b-cell-receptor-pathway-inhibitors
#1
Floyd Hassenrück, Eva Knödgen, Elisa Göckeritz, Safi Hasan Midda, Verena Vondey, Lars Neumann, Sylvia Herter, Christian Klein, Michael Hallek, Günter Krause
The antibody-dependent cell-mediated cytotoxicity (ADCC) of the anti-CD20 monoclonal antibodies (mAbs) rituximab and obinutuzumab against the cell line Raji and isolated CLL cells and its potential impairment by kinase inhibitors (KI) was determined via lactate dehydrogenase release or calcein retention, respectively, using genetically modified NK92 cells expressing CD16-176V as effector cells. Compared to peripheral blood mononuclear cells, recombinant effector cell lines showed substantial alloreactivity-related cytotoxicity without addition of mAbs but afforded determination of ADCC with reduced interassay variability...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29749403/obinutuzumab-plus-bendamustine-in-previously-untreated-patients-with-cll-a-subgroup-analysis-of-the-green-study
#2
Stephan Stilgenbauer, Veronique Leblond, Robin Foà, Sebastian Böttcher, Osman Ilhan, Wolfgang Knauf, Eva Mikuskova, Christoph Renner, Eugen Tausch, Dariusz Woszczyk, Ekaterina Gresko, Linda Lundberg, Tom Moore, Thea Morris, Susan Robson, Francesc Bosch
GREEN (NCT01905943) is a non-randomized, open-label phase IIIb study investigating obinutuzumab alone or plus chemotherapy in chronic lymphocytic leukemia (CLL). We report a preplanned subgroup analysis of 158 previously untreated CLL patients receiving obinutuzumab-bendamustine (G-B). Patients received six 28-day cycles (C) of G-B: obinutuzumab day (D)1/D2 of C1 (25 mg D1/975 mg D2), 1000 mg D8 and D15 of C1, and D1 of C2-6; and bendamustine 70/90 mg/m2 D1 and D2 of C1-6. The primary endpoint was safety/tolerability...
April 27, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29741753/a-tale-of-two-antibodies-obinutuzumab-versus-rituximab
#3
REVIEW
Ciara L Freeman, Laurie H Sehn
While rituximab has dramatically improved outcomes for patients with CD20+ malignancies for two decades, responses are not universal and resistance can develop. Obinutuzumab was developed to potentiate activity and overcome resistance. Pre-clinical data suggests obinutuzumab is superior to rituximab at effecting B cell depletion; however recent phase III clinical trial results have been mixed. The decision of which antibody to employ will probably be further complicated by the approval of a subcutaneous preparation of rituximab and several anti-CD20 biosimilars...
May 9, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29716920/cd20-tcb-with-obinutuzumab-pretreatment-as-next-generation-treatment-of-hematological-malignancies
#4
Marina Bacac, Sara Colombetti, Sylvia Herter, Johannes Sam, Mario Perro, Stanford Chen, Roberta Bianchi, Sarah Diggelmann, Florian Limani, Ramona Schlenker, Tamara Hüsser, Wolfgang F Richter, Katharine Bray-French, Heather J Hinton, Anna Maria F Giusti, Anne Freimoser-Grundschober, Laurent Larivière, Christiane Neumann, Christian Klein, Pablo Umana
PURPOSE: Despite promising clinical activity, T cell engaging therapies including T cell bispecific antibodies (TCBs) are associated with severe side effects requiring the use of step-up-dosing (SUD) regimens to mitigate safety. Here, we present a next generation CD20-targeting TCB (CD20-TCB) with significantly higher potency and a novel approach enabling safer administration of such potent drug. EXPERIMENTAL DESIGN: We developed CD20-TCB based on the 2:1 TCB molecular format and characterized its activity pre-clinically...
May 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29629397/obinutuzumab-a-potent-anti-b-cell-agent-for-rituximab-unresponsive-igm-anti-mag-neuropathy
#5
Goran Rakocevic, Ubaldo Martinez-Outschoorn, Marinos C Dalakas
No abstract text is available yet for this article.
July 2018: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/29623625/applying-a-multicriteria-decision-analysis-mcda-approach-to-elicit-stakeholders-preferences-in-italy-the-case-of-obinutuzumab-for-rituximab-refractory-indolent-non-hodgkin-lymphoma-inhl
#6
Martina Garau, Grace Hampson, Nancy Devlin, Nicola Amedeo Mazzanti, Antonio Profico
BACKGROUND: Healthcare decision makers need to make trade-offs between different elements of value of new treatments. Multicriteria decision analysis (MCDA) provides a framework that can help decision makers to understand stakeholders' preferences and be explicit about the trade-offs that are being made. OBJECTIVE: The objective of this study was to use MCDA to obtain preferences and views on decision criteria across three stakeholder groups (patients, clinicians and payers) in Italy and to use these to assess the performance of obinutuzumab for rituximab-refractory indolent non-Hodgkin lymphoma (iNHL)...
August 22, 2017: PharmacoEconomics open
https://www.readbyqxmd.com/read/29617050/transient-antagonism-of-anti-cd20-monoclonal-antibodies-and-pi3k-inhibitor-idelalisib-in-dlbcl-cell-lines
#7
Anna-Katharina Zoellner, Nico Peter, Yvonne Zimmermann, Grit Hutter, Wolfgang Hiddemann, Martin Dreyling
INTRODUCTION: PI3K inhibitors are evaluated for relapsed and refractory DLBCL patients. OBJECTIVE: Since rituximab has shown to influence BCR-signaling, we investigated the interaction of anti-CD20 antibody rituximab and the new type II glycoengineered anti-CD20 antibody obinutuzumab in combination with the PI3K delta inhibitor idelalisib. METHODS: Established DLBCL cell lines were treated with either rituximab or obinutuzumab alone, or in combination with PI3K delta inhibitor idelalisib...
April 4, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29594951/obinutuzumab-with-bendamustine-for-treating-follicular-lymphoma-refractory-to-rituximab-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#8
REVIEW
Rachid Rafia, Abdullah Pandor, Sarah Davis, John W Stevens, Sue Harnan, Mark Clowes, Youssef Sorour, Robert Cutting
As part of its single technology appraisal process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of obinutuzumab (Roche) to submit evidence on its clinical and cost effectiveness when used in combination with bendamustine in patients with follicular lymphoma (FL) refractory to rituximab. The Evidence Review Group (ERG), the School of Health and Related Research Technology Appraisal Group at the University of Sheffield, produced a document summarising the key points from the company submission alongside a critical review...
March 28, 2018: PharmacoEconomics
https://www.readbyqxmd.com/read/29584548/overall-survival-benefit-in-patients-with-rituximab-refractory-indolent-non-hodgkin-lymphoma-who-received-obinutuzumab-plus-bendamustine-induction-and-obinutuzumab-maintenance-in-the-gadolin-study
#9
Bruce D Cheson, Neil Chua, Jiri Mayer, Greg Dueck, Marek Trněný, Kamal Bouabdallah, Nathan Fowler, Vincent Delwail, Oliver Press, Gilles Salles, John G Gribben, Anne Lennard, Pieternella J Lugtenburg, Günter Fingerle-Rowson, Federico Mattiello, Andrea Knapp, Laurie H Sehn
Purpose To perform an updated analysis of the randomized phase III GADOLIN trial in patients with rituximab-refractory indolent non-Hodgkin lymphoma treated with obinutuzumab (GA101; G) and bendamustine (B). Patients and Methods Patients with histologically documented, rituximab-refractory CD20+ indolent non-Hodgkin lymphoma received G 1,000 mg (days 1, 8, and 15, cycle 1; day 1, cycles 2 to 6) plus B 90 mg/m2 /d (days 1 and 2, all cycles) or B 120 mg/m2 /d monotherapy. Patients who did not experience disease progression with G-B received G maintenance (1,000 mg every 2 months) for up to 2 years...
March 27, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29562857/obinutuzumab-induces-depletion-of-nk-cells-in-patients-with-chronic-lymphocytic-leukemia
#10
Ricardo García-Muñoz, Lorea Aguinaga, Jesus Feliu, Judit Anton-Remirez, Lorena Jorge-Del-Val, Andrea Casajús-Navasal, María José Nebot-Villacampa, Isabel Daroca-Fernandez, Elena Domínguez-Garrido, Pilar Rabasa, Carlos Panizo
AIM: Obinutuzumab induces NK cell antibody-dependent cell-mediated cytotoxicity. OBJECTIVE: Investigate the effects on the human immune system after obinutuzumab monotherapy treatment in patients with chronic lymphocytic leukemia (CLL). METHOD: To evaluate these effects, we analyzed the distribution of CD4+ and CD8+ T cells, B cells and NK cells in the peripheral blood of eight CLL patients who were treated with obinutuzumab in monotherapy...
March 1, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29465308/cll2-bxx-phase-ii-trials-sequential-targeted-treatment-for-eradication-of-minimal-residual-disease-in-chronic-lymphocytic-leukemia
#11
Paula Cramer, Julia von Tresckow, Jasmin Bahlo, Anja Engelke, Petra Langerbeins, Anna-Maria Fink, Kirsten Fischer, Clemens-Martin Wendtner, Karl-Anton Kreuzer, Stephan Stilgenbauer, Sebastian Böttcher, Barbara Eichhorst, Michael Hallek
AIM: Four Phase II trials (clinical trials numbers: NCT02345863, NCT02401503, NCT02445131 and NCT02689141) evaluate a different combination of targeted agents in an all-comer population of approximately 60 patients with chronic lymphocytic leukemia irrespective of prior treatment, physical fitness and genetic risk factors. Patients with a higher tumor load start with a debulking treatment with bendamustine. The subsequent induction and maintenance treatment with an anti-CD20 antibody (obinutuzumab or ofatumumab) and a targeted oral agent (ibrutinib, idelalisib or venetoclax) are continued until achievement of a complete response and minimal residual disease negativity...
March 2018: Future Oncology
https://www.readbyqxmd.com/read/29453281/the-pi3k%C3%AE-selective-inhibitor-idelalisib-minimally-interferes-with-immune-effector-function-mediated-by-rituximab-or-obinutuzumab-and-significantly-augments-b-cell-depletion-in-vivo
#12
Adam Palazzo, Sylvia Herter, Laura Grosmaire, Randy Jones, Christian R Frey, Florian Limani, Marina Bacac, Pablo Umana, Robert J Oldham, Michael J E Marshall, Kerry L Cox, Anna H Turaj, Mark S Cragg, Christian Klein, Matthew J Carter, Stacey Tannheimer
Idelalisib is a highly selective oral inhibitor of PI3Kδ indicated for the treatment of patients with relapsed chronic lymphocytic leukemia in combination with rituximab. Despite additive clinical effects, previous studies have paradoxically demonstrated that targeted therapies potentially negatively affect anti-CD20 mAb effector mechanisms. To address these potential effects, we investigated the impact of PI3Kδ inhibition by idelalisib on the effector mechanisms of rituximab and obinutuzumab. At clinically relevant concentrations, idelalisib minimally influenced rituximab- and obinutuzumab-mediated Ab-dependent cellular cytotoxicity and phagocytosis on human lymphoma cell lines, while maintaining the superiority of obinutuzumab-mediated Ab-dependent cellular cytotoxicity...
April 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29450588/response-rates-and-recurrence-patterns-after-low-dose-radiotherapy-with-4-gy-in-patients-with-low-grade-lymphomas
#13
Laila König, Juliane Hörner-Rieber, Denise Bernhardt, Adriane Hommertgen, Stefan Rieken, Jürgen Debus, Klaus Herfarth
PURPOSE: Retrospective study of effectiveness, toxicity, and relapse patterns after low-dose radiotherapy (LDRT) in patients with low-grade lymphomas. METHODS: 47 patients (median age 64 years) with 50 lesions were treated with LDRT (2 × 2 Gy). In 60%, LDRT was the primary and curative treatment, in 40% offered as second-line therapy in recurrent disease. Histology included follicular (57%) and marginal zone lymphomas (43%). Patients were followed-up regularly clinically (skin) and with CT or MRI scans...
May 2018: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/29443503/dual-color-bioluminescent-sensor-proteins-for-therapeutic-drug-monitoring-of-antitumor-antibodies
#14
Martijn van Rosmalen, Yan Ni, Daan F M Vervoort, Remco Arts, Susann K J Ludwig, Maarten Merkx
Monitoring the levels of therapeutic antibodies in individual patients would allow patient-specific dose optimization, with the potential for major therapeutic and financial benefits. Our group recently developed a new platform of bioluminescent sensor proteins (LUMABS; LUMinescent AntiBody Sensor) that allow antibody detection directly in blood plasma. In this study, we targeted four clinically important therapeutic antibodies, the Her2-receptor targeting trastuzumab, the anti-CD20 antibodies rituximab and obinutuzumab, and the EGFR-blocking cetuximab...
March 6, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29398648/cost-effectiveness-of-ibrutinib-compared-with-obinutuzumab-with-chlorambucil-in-untreated-chronic-lymphocytic-leukemia-patients-with-comorbidities-in-the-united-kingdom
#15
Richa Sinha, William Ken Redekop
BACKGROUND: Ibrutinib shows superiority over obinutuzumab with chlorambucil (G-Clb) in untreated patients with chronic lymphocytic leukemia with comorbidities who cannot tolerate fludarabine-based therapy. However, ibrutinib is relatively more expensive than G-Clb. In this study we evaluated the cost-effectiveness of ibrutinib compared with G-Clb from the United Kingdom (UK) health care perspective. MATERIALS AND METHODS: A 3-state semi-Markov model was parameterized to estimate the lifetime costs and benefits associated with ibrutinib compared with G-Clb as first-line treatment...
February 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29371955/a-comparative-global-phosphoproteomics-analysis-of-obinutuzumab-ga101-versus-rituximab-rtx-against-rtx-sensitive-and-resistant-burkitt-lymphoma-bl-demonstrates-differential-phosphorylation-of-signaling-pathway-proteins-after-treatment
#16
Aradhana Awasthi, Delphine C M Rolland, Janet Ayello, Carmella van de Ven, Venkatesha Basrur, Kevin Conlon, Damian Fermin, Matthew J Barth, Christian Klein, Kojo S J Elenitoba-Johnson, Megan S Lim, Mitchell S Cairo
We recently demonstrated that obinutuzumab (GA101), a novel glycoengineered type II CD20 Ab compared to rituximab (RTX) mediates significantly enhanced antibody-dependent cell cytotoxicity (ADCC) in vitro and increased overall survival in a Burkitt lymphoma (BL) xenograft non-obese diabetic severe combined immunodeficiency gamma (NSG) model. In this study we compared the phosphoproteomic changes by pathway analysis following obinutuzumab vs RTX against RTX-sensitive (Raji) and -resistant BL (Raji4RH). Phosphoproteomic analyses were performed by mass-spectrometry (MS)-based label-free quantitative phosphoproteomic profiling...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348316/evaluation-of-next-generation-anti-cd20-antibodies-labeled-with-zirconium-89-in-human-lymphoma-xenografts
#17
Jason T Yoon, Mark S Longtine, Bernadette V Marquez-Nostra, Richard L Wahl
Radioimmunotherapies with monoclonal antibodies (mAbs) to the B-lymphocyte antigen 20 (CD20) are effective treatments for B-cell lymphomas, but United States Food and Drug Administration (FDA)-approved radioimmunotherapies exclusively use radiolabeled murine antibodies, potentially limiting re-dosing. The FDA recently approved two unlabeled anti-CD20 monoclonal antibodies, obinutizumab and ofatumumab, termed "next generation" as they are humanized (obinituzumab) or fully human (ofatumumab), thus potentially allowing a greater potential for re-dosing than with previous generation anti-CD20 antibodies, including rituximab (chimeric) and tositumumab (murine) which contain more murine peptide sequences...
January 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29324849/the-b-cell-death-function-of-obinutuzumab-hdel-produced-in-plant-nicotiana-benthamiana-l-is-equivalent-to-obinutuzumab-produced-in-cho-cells
#18
Jin Won Lee, Woon Heo, Jinu Lee, Narae Jin, Sei Mee Yoon, Ki Youl Park, Eun Yu Kim, Woo Taek Kim, Joo Young Kim
Plants have attracted attention as bio-drug production platforms because of their economical and safety benefits. The preliminary efficacy of ZMapp, a cocktail of antibodies produced in N. benthamiana (Nicotiana benthamiana L.), suggested plants may serve as a platform for antibody production. However, because the amino acid sequences of the Fab fragment are diverse and differences in post-transcriptional processes between animals and plants remain to be elucidated, it is necessary to confirm functional equivalence of plant-produced antibodies to the original antibody...
2018: PloS One
https://www.readbyqxmd.com/read/29284380/potential-cost-savings-by-dose-down-rounding-of-monoclonal-antibodies-in-a-community-cancer-center
#19
Mehmet S Copur, Curtis Gnewuch, Megan Schriner, Mark Tharnish, Mithat Gonen, Monica McDonald, Jami Kezeor, Ryan C Ramaekers, Dron Gauchan, Douglas Clark, Lois Greenwalt, Mary Mickey, Max Norvell
Purpose Increasing new cancer cases and approval of effective but expensive new drugs extending survival have led to unsustainable cancer care costs. Potential cost savings by a hypothetical dose down-rounding project of monoclonal antibodies at a community-based cancer center is presented. Methods From October 2014 through October 2015, metastatic cancer patients receiving monoclonal antibodies at CHI-Health St Francis Cancer Treatment Center in Grand Island, Nebraska, were identified through electronic health records...
March 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29249186/obinutuzumab-monotherapy-in-previously-untreated-chronic-lymphocytic-leukemia
#20
Nathan D Gay, Eliana Kozin, Craig Okada, Alexey V Danilov, Stephen Spurgeon
No abstract text is available yet for this article.
December 18, 2017: Leukemia & Lymphoma
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