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Obinutuzumab

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https://www.readbyqxmd.com/read/28072473/pharmacokinetics-of-obinutuzumab-in-chinese-patients-with-b-cell-lymphomas
#1
John Zhai, Yan Qin, Jun Zhu, Yuqin Song, Zhixiang Shen, Xin Du, Candice Jamois, Michael Brewster, Yuankai Shi, Jun Shi
AIM: The Phase Ib GERSHWIN study (NCT01680991) assessed the pharmacokinetic (PK) profile of obinutuzumab following multiple intravenous (i.v.) doses to Chinese patients with B-cell lymphomas, and compared findings with previous obinutuzumab PK studies in mainly Caucasian (non-Chinese) patients. METHODS: GERSHWIN was an open-label, single-arm intervention study. Patients aged >18 years with CD20+ relapsed/refractory chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) were enrolled from four centres in China...
January 10, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28011903/safety-and-efficacy-of-obinutuzumab-with-chop-or-bendamustine-in-previously-untreated-follicular-lymphoma
#2
Andrew Grigg, Martin J S Dyer, Marcos González Díaz, Martin Dreyling, Simon Rule, Guiyuan Lei, Andrea Knapp, Elisabeth Wassner-Fritsch, Paula Marlton
The GAUDI study assessed safety and preliminary efficacy of induction therapy with obinutuzumab plus chemotherapy, followed by maintenance with obinutuzumab alone, in previously untreated patients with follicular lymphoma. Assignment to chemotherapy was decided on a per center basis before patient enrollment. Patients (n=81) received 4-6 cycles of obinutuzumab plus bendamustine every 4 weeks or 6-8 cycles of obinutuzumab plus CHOP every 3 weeks. Patients with an end-of-treatment response were eligible for obinutuzumab maintenance therapy every 3 months for 2 years or until disease progression...
December 23, 2016: Haematologica
https://www.readbyqxmd.com/read/28004361/a-review-of-obinutuzumab-ga101-a-novel-type-ii-anti-cd20-monoclonal-antibody-for-the-treatment-of-patients-with-b-cell-malignancies
#3
REVIEW
Kensei Tobinai, Christian Klein, Naoko Oya, Günter Fingerle-Rowson
Obinutuzumab (GA101) is a novel, type II, glycoengineered, humanized anti-CD20 monoclonal antibody that has been developed to address the need for new therapeutics with improved efficacy in patients with lymphocytic leukemia and lymphoma of B-cell origin. Obinutuzumab has a distinct mode of action relative to type I anti-CD20 antibodies, such as rituximab, working primarily by inducing direct cell death and antibody-dependent cell-mediated cytotoxicity. Obinutuzumab is under investigation in a wide-ranging program of clinical trials in patients with B-cell malignancies...
December 21, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27971697/budget-impact-analysis-of-obinutuzumab-and-ibrutinib-in-patients-with-chronic-lymphocytic-leukemia-in-russia
#4
E V Derkach, O Y Rebrova, V K Fedyaeva
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27913471/sequencing-of-chronic-lymphocytic-leukemia-therapies
#5
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/27900446/health-related-quality-of-life-and-symptoms-in-patients-with-rituximab-refractory-indolent-non-hodgkin-lymphoma-treated-in-the-phase-iii-gadolin-study-with-obinutuzumab-plus-bendamustine-versus-bendamustine-alone
#6
Bruce D Cheson, Peter C Trask, John G Gribben, Natalie Dimier, Eva Kimby, Pieternella J Lugtenburg, Catherine Thieblemont, Elisabeth Wassner-Fritsch, Aino Launonen, Laurie H Sehn
We present health-related quality of life (HRQoL) data from GADOLIN, comparing bendamustine (B) alone or combined with obinutuzumab (G-B) in rituximab-refractory indolent non-Hodgkin lymphoma patients. The Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) questionnaire was administered on day 1 of cycles 1, 3, and 5 during treatment, at end of induction (EOI), bi-monthly for 2 years during maintenance/follow-up, and annually during extended follow-up until progression/death. Time to first ≥6-point worsening from baseline in the FACT-Lym trial outcome index (TOI) was estimated...
November 30, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27892987/sweet-like-eruption-associated-with-obinutuzumab-therapy-for-chronic-lymphocytic-leukemia
#7
Abraham M Korman, Justin G Hastings, John C Byrd, Benjamin H Kaffenberger
No abstract text is available yet for this article.
January 1, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/27890931/a-tlr7-agonist-enhances-the-antitumor-efficacy-of-obinutuzumab-in-murine-lymphoma-models-via-nk-cells-and-cd4-t-cells
#8
E J Cheadle, G Lipowska-Bhalla, S J Dovedi, E Fagnano, C Klein, J Honeychurch, T M Illidge
Anti-CD20 monoclonal antibodies (mAb) such as rituximab have been proven to be highly effective at improving outcome in B-cell malignancies. However, many patients ultimately relapse and become refractory to treatment. The glycoengineered anti-CD20 mAb obinutuzumab was developed to induce enhanced antibody-dependent cellular cytotoxicity, antibody-dependent phagocytosis and direct cell death and was shown to lead to improved outcomes in a randomized study in B-CLL. We hypothesized that immune stimulation through Toll-like receptor 7 (TLR7) agonism in combination with obinutuzumab would further enhance lymphoma clearance and the generation of long-term antitumor immune responses...
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27854102/the-next-generation-of-targeted-molecules-for-the-treatment-of-chronic-lymphocytic-leukemia
#9
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/27748757/increased-fc%C3%AE-riib-dominance-contributes-to-the-emergence-of-resistance-to-therapeutic-antibodies-in-chronic-lymphocytic-leukaemia-patients
#10
M Burgess, S Mapp, R Mazzieri, C Cheung, L Chambers, S R Mattarollo, P Mollee, D Gill, N A Saunders
Resistance to therapeutic antibodies in chronic lymphocytic leukaemia (CLL) is common. In this study, we show that therapeutic antibodies against CD62L (CD62L-Ab) or CD20 (obinutuzumab) were able to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis (ADP) in primary cultures of CLL cells. CLL cells derived from patients with active disease requiring treatment displayed resistance to these antibodies, whereas patients with stable disease were sensitive. Using enrichment strategies and transcriptomic analyses, we show that antibody-dependent tumour cell killing was FcγR-dependent and mediated by macrophages...
October 17, 2016: Oncogene
https://www.readbyqxmd.com/read/27742065/current-strategies-to-create-tailored-and-risk-adapted-therapies-for-cll-patients
#11
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/27703384/economic-evaluation-of-obinutuzumab-in-combination-with-chlorambucil-in-first-line-treatment-of-patients-with-chronic-lymphocytic-leukemia-in-spain
#12
Luis Felipe Casado, Amparo Burgos, Eva González-Haba, Javier Loscertales, Tania Krivasi, Javier Orofino, Carlos Rubio-Terres, Darío Rubio-Rodríguez
OBJECTIVE: To evaluate the cost-effectiveness of obinutuzumab in combination with chlorambucil (GClb) versus rituximab plus chlorambucil (RClb) in the treatment of adults with previously untreated chronic lymphocytic leukemia (CLL) and with comorbidities that make them unsuitable for full-dose fludarabine-based therapy, from the perspective of the Spanish National Health System. METHODS: A Markov model was developed with three mutually exclusive health states: progression-free survival (with or without treatment), progression, and death...
2016: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/27698437/intravital-imaging-reveals-improved-kupffer-cell-mediated-phagocytosis-as-a-mode-of-action-of-glycoengineered-anti-cd20-antibodies
#13
Capucine L Grandjean, Fabricio Montalvao, Susanna Celli, David Michonneau, Beatrice Breart, Zacarias Garcia, Mario Perro, Olivier Freytag, Christian A Gerdes, Philippe Bousso
Anti-CD20 monoclonal antibodies (mAbs) represent an effective treatment for a number of B cell malignancies and autoimmune disorders. Glycoengineering of anti-CD20mAb may contribute to increased anti-tumor efficacy through enhanced antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADP) as reported by in vitro studies. However, where and how glycoengineered Ab may potentiate therapeutic responses in vivo is yet to be elucidated. Here, we have performed mouse liver transplants to demonstrate that the liver is sufficient to mediate systemic B cells depletion after anti-CD20 treatment...
October 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27697772/rational-targeted-therapies-to-overcome-microenvironment-dependent-expansion-of-mantle-cell-lymphoma
#14
David Chiron, Céline Bellanger, Antonin Papin, Benoit Tessoulin, Christelle Dousset, Sophie Maiga, Anne Moreau, Julie Esbelin, Valérie Trichet, Selina Chen-Kiang, Philippe Moreau, Cyrille Touzeau, Steven Le Gouill, Martine Amiot, Catherine Pellat-Deceunynck
Mantle cell lymphoma (MCL) accumulates in lymphoid organs, but disseminates early on in extranodal tissues. Although proliferation remains located in lymphoid organs only, suggesting a major role of the tumor ecosystem, few studies have assessed MCL microenvironment. We therefore cocultured primary circulating MCL cells from 21 patients several weeks ex vivo with stromal or lymphoid-like (CD40L) cells to determine which interactions could support their proliferation. We showed that coculture with lymphoid-like cells, but not stromal cells, induced cell-cycle progression, which was amplified by MCL-specific cytokines (insulin-like growth factor-1, B-cell activating factor, interleukin-6, interleukin-10)...
December 15, 2016: Blood
https://www.readbyqxmd.com/read/27684575/anti-tumor-efficacy-study-of-the-bruton-s-tyrosine-kinase-btk-inhibitor-ono-gs-4059-in-combination-with-the-glycoengineered-type-ii-anti-cd20-monoclonal-antibody-obinutuzumab-ga101-demonstrates-superior-in-vivo-efficacy-compared-to-ono-gs-4059-in-combination
#15
Tomoko Yasuhiro, Wako Sawada, Christian Klein, Ryohei Kozaki, Shingo Hotta, Toshio Yoshizawa
The activated B-cell diffuse large B-cell-like lymphoma (ABC-DLBCL) correlates with poor prognosis. The B-cell receptor signaling pathway is known to be dysregulated in NHL/CLL and given BTK is a downstream mediator of BCR signaling, BTK constitutes an interesting and obvious therapeutic target. Given the high potency and selectivity of the BTK inhibitor, ONO/GS-4059, it was hypothesized that, the anti-tumor activity of ONO/GS-4059 could be further enhanced by combining it with the anti-CD20 Abs, rituximab (RTX) or obinutuzumab (GA101)...
August 9, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27630351/lymphoma-of-the-cervix-case-report-and-review-of-the-literature
#16
Ziad Hilal, Franziska Hartmann, Askin Dogan, Cem Cetin, Harald Krentel, Sven Schiermeier, Beate Schultheis, Clemens B Tempfer
BACKGROUND: Lymphoma of the uterine cervix (LUCX) is rare and may occur as a primary or secondary manifestation of this disease. Clinical and cytological presentations of LUCX vary and establishing diagnosis is often difficult. Surgery followed by radiation or chemotherapy is the mainstay of treatment. CASE REPORT: We present the case of a 73-year-old woman with recurrent pathological PAP smears of the cervix and a history of chronic lymphatic leukemia 15 years ago...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27605883/prevention-and-management-of-hepatitis-b-virus-reactivation-in-patients-with-hematological-malignancies-treated-with-anticancer-therapy
#17
REVIEW
Man Fai Law, Rita Ho, Carmen K M Cheung, Lydia H P Tam, Karen Ma, Kent C Y So, Bonaventure Ip, Jacqueline So, Jennifer Lai, Joyce Ng, Tommy H C Tam
Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc)...
July 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27535291/a-systematic-review-and-network-meta-analysis-to-evaluate-the-comparative-efficacy-of-interventions-for-unfit-patients-with-chronic-lymphocytic-leukemia
#18
Nicolas Städler, Aijing Shang, Francesc Bosch, Andrew Briggs, Valentin Goede, Aurelien Berthier, Corinne Renaudin, Veronique Leblond
INTRODUCTION: Rituximab plus fludarabine and cyclophosphamide (RFC) is the standard of care for fit patients with untreated chronic lymphocytic leukemia (CLL); however, its use is limited in 'unfit' (co-morbid and/or full-dose F-ineligible) patients due to its toxicity profile. We conducted a systematic review and Bayesian network meta-analysis (NMA) to determine the relative efficacy of commercially available interventions for the first-line treatment of unfit CLL patients. METHODS: For inclusion in the NMA, studies had to be linked via common treatment comparators, report progression-free survival (PFS), and/or overall survival (OS), and meet at least one of the five inclusion criteria: median cumulative illness score >6, median creatinine clearance ≤70 mL/min, existing co-morbidities, median age ≥70 years, and no full-dose F in the comparator arm...
October 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27528699/complement-regulatory-proteins-cfhr1-and-cfhr3-and-patient-response-to-anti-cd20-monoclonal-antibody-therapy
#19
Laura M Rogers, Sarah L Mott, Brian Smith, Brian K Link, Deniz Sahin, George J Weiner
PURPOSE: Anti-CD20 monoclonal antibody (mAb) therapies, including rituximab and obinutuzumab (GA101) are common treatments for follicular lymphoma (FL). In an effort to better understand the role of complement in mAb action, we recently performed germline SNP profiling on 142 FL patients and found rs3766404 genotype correlated with patient response to rituximab. To assess the role of three SNP-associated complement regulatory proteins (CFH, CFHR1 and CFHR3) in clinical response to anti-CD20 mAb, we studied two cohorts of patients treated with anti-CD20 mAb...
August 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27521873/new-monoclonal-antibodies-for-the-treatment-of-acute-lymphoblastic-leukemia
#20
REVIEW
Nosha Farhadfar, Mark R Litzow
Monoclonal antibodies represent a major advance in treatment of acute lymphoblastic leukemia (ALL). Targeted delivery of these agents based on leukemic cell-surface receptor recognition, improves efficacy and minimizes off-target toxicity. The antigens CD19, CD20, CD22 and CD52, are the most common antigens to which monoclonal antibodies in B-cell ALL have been directed. Rituximab, an anti-CD20 antibody, in combination with conventional chemotherapy has been shown to improve survival in newly diagnosed CD20 positive B-cell ALL...
October 2016: Leukemia Research
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