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Obinutuzumab

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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
#1
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
#2
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
#3
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
#4
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...
September 11, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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...
August 10, 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
#11
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
https://www.readbyqxmd.com/read/28766542/-efficacy-of-a-bendamustine-and-rituximab-combination-in-first-line-therapy-for-chronic-lymphocytic-leukemia-results-of-the-ben-001-study
#12
E A Stadnik, V V Strugov, T O Andreeva, Yu V Virts, A M Rumyantsev, Yu V Mirolyubova, P A Butylin, A Yu Zaritsky
AIM: To evaluate the efficacy and safety of the BR regimen containing bendamustine in patients with chronic lymphocytic leukemia (CLL) who have not previously received specific therapy. SUBJECTS AND METHODS: The results of the Russian prospective observational multicenter study BEN-001 (2012-2015) covering 196 CLL patients from 34 centers of the Russian Federation were analyzed. The diagnosis was confirmed by the results of peripheral blood lymphocyte immunophenotyping...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28751765/a-tlr7-agonist-enhances-the-antitumor-efficacy-of-obinutuzumab-in-murine-lymphoma-models-via-nk-cells-and-cd4-t-cells
#13
E J Cheadle, G Lipowska-Bhalla, S J Dovedi, E Fagnano, C Klein, J Honeychurch, T M Illidge
This corrects the article DOI: 10.1038/leu.2016.352.
July 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28747208/ga101-obinutuzumab-monoclonal-antibody-as-consolidation-therapy-in-cll-galactic-trial-study-protocol-for-a-phase-ii-iii-randomised-controlled-trial
#14
Jamie B Oughton, Laura Collett, Dena R Howard, Anna Hockaday, Talha Munir, Kathryn McMahon, Lucy McParland, Claire Dimbleby, David Phillips, Andy C Rawstron, Peter Hillmen
BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia. Achieving minimal residual disease (MRD) negativity in CLL is an independent predictor of survival even with a variety of different treatment approaches and regardless of the line of therapy. METHODS/DESIGN: GA101 (obinutuzumab) monocLonal Antibody as Consolidation Therapy In CLL (GALACTIC) is a seamless phase II/III, multi-centre, randomised, controlled, open, parallel-group trial for patients with CLL who have recently responded to chemotherapy...
July 26, 2017: Trials
https://www.readbyqxmd.com/read/28710251/role-for-zap-70-signaling-in-the-differential-effector-functions-of-rituximab-and-obinutuzumab-ga101-in-chronic-lymphocytic-leukemia-b-cells
#15
Sladjana Skopelja-Gardner, Jonathan D Jones, B JoNell Hamilton, Alexey V Danilov, William F C Rigby
Rituximab (RTX) has been the hallmark anti-CD20 mAb for the treatment of B cell neoplasms, including B cell chronic lymphocytic leukemia (B-CLL). Recently, a novel humanized anti-CD20 mAb obinutuzumab (GA101) has been implemented as first-line CLL therapy. Treatment of CLL patients with RTX is associated with CD20 loss via an FcγR-mediated process, trogocytosis. RTX-induced trogocytosis has been characterized as both the means of resistance to therapy, via loss of cell surface target proteins (antigenic modulation), as well as a process that alters B cell phenotype and function...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28705863/fischer-k-al-sawaf-o-fink-a-m-et-al-venetoclax-and-obinutuzumab-in-chronic-lymphocytic-leukemia-blood-2017-129-19-2702-2705
#16
(no author information available yet)
No abstract text is available yet for this article.
July 13, 2017: Blood
https://www.readbyqxmd.com/read/28685928/management-of-patients-with-previously-untreated-chronic-lymphocytic-leukaemia-with-obinutuzumab-and-chlorambucil
#17
REVIEW
Constantine Tam, Bryone Kuss, Stephen Opat, Joy Boulos, Paula Marlton
Patients with chronic lymphocytic leukaemia (CLL) are generally older, with many considered 'unfit' for fludarabine-cyclophosphamide-rituximab therapy. In these patients, the combination of obinutuzumab-chlorambucil may be an appropriate therapeutic choice. Obinutuzumab-chlorambucil has been demonstrated to improve overall survival rates compared to chlorambucil alone and to improve progression-free survival and overall response rates compared to rituximab-chlorambucil. This combination can lead to certain toxicities that need to be addressed through appropriate patient selection, pre-medication and management...
July 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28592762/chronic-lymphocytic-leukemia-pathophysiology-and-current-therapy
#18
Jun Takizawa
Chronic lymphocytic leukemia (CLL) is the most frequent adult leukemia in western countries, but it is rare in Japan. Several mutations have been identified in patients with CLL using next-generation sequencing, but disease-specific mutations were not found. Some mutations, such as those in TP53, NOTCH1, SF3B, and BIRC3 are useful for risk stratification and prognosis prediction in patients with CLL. Strategies for treating CLL are rapidly evolving, with targeted agents such as the B-cell receptor signaling pathway inhibitors (ibrutinib, idelalisib), novel anti-CD20 monoclonal antibody (obinutuzumab), and Bcl-2 inhibitor (venetoclax) being approved by the US Food and Drug Administration...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28588833/obinutuzumab-induced-serum-sickness-following-salvage-therapy-for-chronic-lymphocytic-leukemia
#19
Julie Saba, Aaron C Logan
The incidence of serum sickness following treatment of CLL with obinutuzumab has not been fully characterized, but is likely rare. Consideration should be given to this diagnosis in appropriate circumstances so that effective corticosteroid therapy can be initiated to alleviate inflammatory symptoms and organ dysfunction in a timely manner.
June 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28584371/shifting-focus-in-the-therapeutics-of-immunobullous-disease
#20
Abhishek De, Asad Ansari, Nidhi Sharma, Aarti Sarda
Therapeutics of autoimmune bullous disease has seen a major shift of focus from more global immunosuppression to targeted immunotherapy. Anti CD 20 monoclonal antibody Rituximab revolutionized the therapeutics of autoimmune bullous disease particularly pemphigus. Though it is still being practiced off-label, evidences in the form of RCT and meta analysis are now available. Other novel anti CD 20 monoclonal antibodies like ofatumumab, veltuzumab, and ocrelizumab, tositumomab or obinutuzumab/GA101 may add to the therapeutic options in coming days...
May 2017: Indian Journal of Dermatology
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