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Obinutuzumab

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https://www.readbyqxmd.com/read/29143151/next-generation-anti-cd20-monoclonal-antibodies-in-autoimmune-disease-treatment
#1
Fanny Huynh Du, Elizabeth A Mills, Yang Mao-Draayer
The clinical success of anti-CD20 monoclonal antibody (mAb)-mediated B cell depletion therapy has contributed to the understanding of B cells as major players in several autoimmune diseases. The first therapeutic anti-CD20 mAb, rituximab, is a murine-human chimera to which many patients develop antibodies and/or experience infusion-related reactions. A second generation of anti-CD20 mAbs has been designed to be more effective, better tolerated, and of lower immunogenicity. These include the humanized versions: ocrelizumab, obinutuzumab, and veltuzumab, and the fully human, ofatumumab...
November 16, 2017: Auto- Immunity Highlights
https://www.readbyqxmd.com/read/29113954/an-improved-method-to-quantify-human-nk-cell-mediated-antibody-dependent-cell-mediated-cytotoxicity-adcc-per-igg-fcr-positive-nk-cell-without-purification-of-nk-cells
#2
Alexander P Sung, Jennifer J-J Tang, Michael J Guglielmo, Doug Redelman, Julie Smith-Gagen, Lucinda Bateman, Dorothy Hudig
Natural killer (NK) lymphocyte ADCC supports anti-viral protection and monoclonal antibody (mAb) anti-tumor therapies. To predict in vivo ADCC therapeutic responses of different individuals, measurement of both ADCC cellular lytic capacity and their NK cellular receptor recognition of antibodies on 'target' cells are needed, using clinically available amounts of blood. Twenty ml of blood provides sufficient peripheral blood mononuclear cells (PBMCs) for the new assay for lytic capacity described here and for an antibody EC50 assay for Fc-receptor recognition...
November 4, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29082795/treatment-approach-for-elderly-and-unfit-patients-with-chronic-lymphocytic-leukemia
#3
Idanna Innocenti, Francesco Autore, Raffaella Pasquale, Francesca Morelli, Dimitar G Efremov, Luca Laurenti
Elderly patients with chronic lymphocytic leukemia (CLL) or patients with comorbidities are often treated with chlorambucil (Chl) as front-line therapy despite relatively low response rates. The addition of a monoclonal anti-CD20 antibody to Chl substantially increases response rates and prolongs progression-free survival (PFS) in these patients, without increasing toxicity. As a result, the ESMO guidelines recommend that previously untreated CLL patients with relevant co-morbidity, but without TP53 deletion/mutation, should be treated with the combination of Chl plus an anti-CD20 antibody (rituximab, ofatumumab or obinutuzumab)...
October 30, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/29079598/ga101-p329g-lala-a-variant-of-obinutuzumab-with-abolished-adcc-adcp-and-cdc-function-but-retained-cell-death-induction-is-as-efficient-as-rituximab-in-b-cell-depletion-and-antitumor-activity
#4
Sylvia Herter, Frank Herting, Gunter Muth, Erwin van Puijenbroek, Tilman Schlothauer, Claudia Ferrara, Kevin Brady, Sabine Lang, Marina Bacac, Ekkehard Mössner, Pablo Umana, Christian Klein
No abstract text is available yet for this article.
October 27, 2017: Haematologica
https://www.readbyqxmd.com/read/29066535/obinutuzumab-effective-in-follicular-lymphoma-but-at-a-cost
#5
(no author information available yet)
In a phase III trial involving more than 1,200 patients with follicular lymphoma, obinutuzumab plus chemotherapy reduced the risk of disease progression, relapse, or death by 34% compared with rituximab plus chemotherapy. However, patients receiving obinutuzumab experienced more serious side effects than those receiving rituximab.
October 24, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29033196/first-line-obinutuzumab-for-follicular-lymphoma
#6
Holly Baker
No abstract text is available yet for this article.
October 12, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29025266/the-abcs-of-immunotherapy-for-adult-patients-with-b-cell-acute-lymphoblastic-leukemia
#7
Troy Z Horvat, Amanda N Seddon, Adebayo Ogunniyi, Amber C King, Larry W Buie, Ryan J Daley
OBJECTIVE: To review the pharmacology, efficacy, and safety of Food and Drug Administration approved and promising immunotherapy agents used in the treatment of acute lymphoblastic leukemia (ALL). DATA SOURCES: A literature search was performed of PubMed and MEDLINE databases (1950 to July 2017) and of abstracts from the American Society of Hematology and the American Society of Clinical Oncology. Searches were performed utilizing the following key terms: rituximab, blinatumomab, inotuzumab, ofatumumab, obinutuzumab, Blincyto, Rituxan, Gazyva, Arzerra, CAR T-cell, and chimeric antigen receptor (CAR)...
October 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28983798/rituximab-in-b-cell-hematologic-malignancies-a-review-of-20-years-of-clinical-experience
#8
REVIEW
Gilles Salles, Martin Barrett, Robin Foà, Joerg Maurer, Susan O'Brien, Nancy Valente, Michael Wenger, David G Maloney
Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma...
October 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28976863/obinutuzumab-for-the-first-line-treatment-of-follicular-lymphoma
#9
RANDOMIZED CONTROLLED TRIAL
Robert Marcus, Andrew Davies, Kiyoshi Ando, Wolfram Klapper, Stephen Opat, Carolyn Owen, Elizabeth Phillips, Randeep Sangha, Rudolf Schlag, John F Seymour, William Townsend, Marek Trněný, Michael Wenger, Günter Fingerle-Rowson, Kaspar Rufibach, Tom Moore, Michael Herold, Wolfgang Hiddemann
BACKGROUND: Rituximab-based immunochemotherapy has improved outcomes in patients with follicular lymphoma. Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody. We compared rituximab-based chemotherapy with obinutuzumab-based chemotherapy in patients with previously untreated advanced-stage follicular lymphoma. METHODS: We randomly assigned patients to undergo induction treatment with obinutuzumab-based chemotherapy or rituximab-based chemotherapy...
October 5, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28928164/immunopet-of-malignant-and-normal-b-cells-with%C3%A2-89-zr-and%C3%A2-124-i-labeled-obinutuzumab-antibody-fragments-reveals-differential-cd20-internalization-in-vivo
#10
Kirstin A Zettlitz, Richard Tavare, Scott M Knowles, Kristopher K Steward, John M Timmerman, Anna M Wu
PURPOSE: The B-cell antigen CD20 provides a target for antibody-based positron emission tomography (immunoPET). We engineered antibody fragments targeting human CD20 and studied their potential as immunoPET tracers in transgenic mice (huCD20TM) and in a murine lymphoma model expressing human CD20. EXPERIMENTAL DESIGN: Anti-CD20 cys-diabody (cDb) and cys-minibody (cMb) based on rituximab (Rx) and obinutuzumab (GA101) were radioiodinated and used for immunoPET imaging of a murine lymphoma model...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28918995/cutaneous-adverse-events-of-targeted-therapies-for-hematolymphoid-malignancies
#11
REVIEW
Julia D Ransohoff, Bernice Y Kwong
The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies...
July 14, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28914567/chemotherapy-free-triple-combination-of-obinutuzumab-venetoclax-and-idasanutlin-antitumor-activity-in-xenograft-models-of-non-hodgkin-lymphoma
#12
Frank Herting, Thomas Friess, Pablo Umaña, Steven Middleton, Christian Klein
No abstract text is available yet for this article.
September 15, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28893099/obinutuzumab-for-the-treatment-of-chronic-lymphocytic-leukemia-and-other-b-cell-lymphoproliferative-disorders
#13
Rabih Said, Apostolia M Tsimberidou
Chemoimmunotherapeutic regimens using the anti-CD20 antibody rituximab improved significantly the survival rates in various B-cell lymphoproliferative disorders (LPDs), including chronic lymphocytic leukemia (CLL). The next-generation CD20 antibody obinutuzumab represents an addition to the drug armamentarium used for the therapeutic management of patients with LPDs. Areas covered: Herein, the authors discuss the biochemical and conformational engineering of obinutuzumab to increase antibody-dependent cell-mediated cytotoxicity and direct cell death...
November 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28870106/expanded-access-to-cancer-treatments-from-conversion-to-neutropenia-prophylaxis-with-biosimilar-filgrastim-sndz
#14
Ali McBride, Sanjeev Balu, Kim Campbell, Mohan Bikkina, Karen MacDonald, Ivo Abraham
AIM: Biosimilar medicines offer significant cost-savings potential over their reference products, which can be re-allocated to provide access to other cancer treatments on a budget-neutral basis. METHODS: Simulation study using cost data for the USA under consideration of several prophylaxis patterns. RESULTS: Potential savings from conversion from reference filgrastim to biosimilar filgrastim-sndz are significant. These savings expand budget-neutral access to novel immunotherapies (obinutuzumab; pembrolizumab) or supportive care (filgrastim-sndz)...
September 5, 2017: Future Oncology
https://www.readbyqxmd.com/read/28869483/obinutuzumab-plus-chlorambucil-in-a-patient-with-severe-myasthenia-gravis-and-chronic-lymphocytic-leukemia
#15
Angela Russell, Megan Yaraskavitch, Daniel Fok, Sameer Chhibber, Lesley Street, Lawrence Korngut
Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction, characterized by fatigable weakness of the extraocular, bulbar, and limb musculature; prevalence is estimated at 14 to 32 per 100,000 in North America. Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, resulting from clonal expansion of B-cells in blood, marrow, and secondary lymphoid tissues. The simultaneous presentation of MG and CLL is exceedingly rare. This article presents the case of 71-year-old man diagnosed simultaneously with MG and CLL...
2017: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/28845710/combination-therapy-with-the-type-ii-anti-cd20-antibody-obinutuzumab
#16
REVIEW
Christian Klein, Marina Bacac, Pablo Umana, Günter Fingerle-Rowson
Obinutuzumab is a novel humanized type II glycoengineered anti-CD20 antibody approved for first-line treatment of chronic lymphocytic leukemia (CLL) in combination with chlorambucil and for treatment of rituximab-refractory follicular lymphoma (FL). Areas covered: We describe current preclinical and clinical evidence supporting the combination of obinutuzumab with not only chemotherapy but also novel targeted therapies for B-cell hematologic malignancies, and its application in chemoimmunotherapy. We also provide an overview of the current clinical trial landscape investigating novel combination therapies based on obinutuzumab...
October 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28830332/hypersensitivity-reactions-to-obinutuzumab-in-cynomolgus-monkeys-and-relevance-to-humans
#17
Elisabeth Husar, Maria Solonets, Olaf Kuhlmann, Eginhard Schick, Hanna Piper-Lepoutre, Thomas Singer, Gaurav Tyagi
Obinutuzumab (GA101, Gazyva™, Gazyvaro®, F. Hoffmann-La Roche AG, Basel, Switzerland) is a humanized, glycoengineered type II antibody targeted against CD20. The preclinical safety evaluation required to support clinical development and marketing authorization of obinutuzumab included repeat-dose toxicity studies in cynomolgus monkeys for up to 6-month dosing with a 9-month recovery period. Results from those studies showed decreases in circulating B cells and corresponding B-cell depletion in lymphoid tissues, consistent with the desired pharmacology of obinutuzumab...
July 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28821272/novel-immunotherapies-for-adult-patients-with-b-lineage-acute-lymphoblastic-leukemia
#18
REVIEW
Guoqing Wei, Jiasheng Wang, He Huang, Yanmin Zhao
The past decade witnessed the rapid development of adult B-lineage acute lymphoblastic leukemia (ALL) treatment. Beyond the development of chemotherapy regimens, immunotherapy is starting a new era with unprecedented complete remission (CR) rate. Targeting B-lineage-specific surface markers such as CD19, CD20, CD22, or CD52, immunotherapy has been demonstrating promising clinical results. Among the immunotherapeutic methods, naked monoclonal antibodies (mAbs), antibody-drug conjugate (ADC), bispecific T cell engager (BiTE), and chimeric antigen receptor (CAR) T cells are the main types...
August 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28796588/obinutuzumab-or-rituximab-plus-cyclophosphamide-doxorubicin-vincristine-and-prednisone-in-previously-untreated-diffuse-large-b-cell-lymphoma
#19
RANDOMIZED CONTROLLED TRIAL
Umberto Vitolo, Marek Trněný, David Belada, John M Burke, Angelo Michele Carella, Neil Chua, Pau Abrisqueta, Judit Demeter, Ian Flinn, Xiaonan Hong, Won Seog Kim, Antonio Pinto, Yuan-Kai Shi, Yoichi Tatsumi, Mikkel Z Oestergaard, Michael Wenger, Günter Fingerle-Rowson, Olivier Catalani, Tina Nielsen, Maurizio Martelli, Laurie H Sehn
Purpose Rituximab (R) plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy is the standard of care in previously untreated diffuse large B-cell lymphoma (DLBCL). Obinutuzumab (G) is a glycoengineered, type II, anti-CD20 monoclonal antibody. GOYA was a randomized phase III study that compared G-CHOP with R-CHOP in patients with previously untreated advanced-stage DLBCL. Methods Patients (N = 1,418) were randomly assigned to receive eight 21-day cycles of G (n = 706) or R (n = 712), plus six or eight cycles of CHOP...
November 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28782884/chronic-lymphocytic-leukemia-2017-update-on-diagnosis-risk-stratification-and-treatment
#20
REVIEW
Michael Hallek
DISEASE OVERVIEW: Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B cells. DIAGNOSIS: The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen and B-cell markers...
September 2017: American Journal of Hematology
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