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Obinutuzumab

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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
#1
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
#2
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...
July 14, 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
#3
(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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28584136/obinutuzumab-what-is-there-to-learn-from-clinical-trials
#8
Guillaume Cartron, Hervé Watier
Obinutuzumab (OBZ) is a recombinant type II anti-CD20 and IgG1 Fc-optimized monoclonal antibody (mAb), recently approved in chronic lymphocytic leukemia (B-CLL) and follicular lymphoma (FL). Rituximab (RTX) is frequently considered as its "ancestor" and OBZ clinical development was justified by the importance of FcγRIIIA-mediated mechanisms in RTX clinical activity. However, RTX differs from OBZ in two critical independent properties, being a type I anti-CD20 mAb, and not being Fc-optimized. Moreover, the use of a different dosing regimen for RTX and OBZ further complicates any interpretation of clinical results...
June 5, 2017: Blood
https://www.readbyqxmd.com/read/28573505/comparative-efficacy-of-ibrutinib-versus-obinutuzumab%C3%A2-%C3%A2-chlorambucil-in-first-line-treatment-of-chronic-lymphocytic-leukemia-a-matching-adjusted-indirect-comparison
#9
Suzy Van Sanden, Simona Baculea, Joris Diels, Sarah Cote
INTRODUCTION: Ibrutinib (ibr) monotherapy and the combination of obinutuzumab plus chlorambucil (obi) are approved for previously untreated chronic lymphocytic leukemia (CLL). No trials directly comparing their efficacy are available. Therefore a matching-adjusted indirect comparison (MAIC) was performed to provide insight into their relative efficacy in terms of progression-free survival (PFS) and overall survival (OS). MAIC attempts to adjust for between-trial differences in factors known or suspected to influence treatment effects, to minimize bias...
July 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28565930/current-perspectives-on-the-role-of-chemotherapy-in-chronic-lymphocytic-leukemia
#10
Clemens-Martin Wendtner, Michael Gregor
Chemotherapy has long been integral to the treatment of chronic lymphocytic leukemia (CLL). Fludarabine/cyclophosphamide, chlorambucil and bendamustine are commonly used as a backbone, depending on the patient's age and general health. The advent of the anti-CD20 monoclonal antibodies, such as rituximab and obinutuzumab, altered the face of treatment, and chemoimmunotherapy still forms the current standard first-line approach. However, the landscape is changing following the emergence of novel targeted agents, such as ibrutinib, idelalisib and venetoclax, which offer the chance for improved efficacy over standard therapy alone, with no substantial increase in toxicity...
June 1, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28516439/reassessment-of-anti-cd20-therapy-in-lymphoid-malignancies-impact-limitations-and-new-directions
#11
REVIEW
Patrick M Reagan, Jonathan W Friedberg
The addition of anti-CD20 monoclonal antibodies to the treatment of B-cell malignancies has dramatically affected the field as well as the lives of patients. Rituximab in particular has been combined safely with conventional chemotherapy and has resulted in improved overall survival in major histologic subtypes of B-cell lymphoma and chronic lymphocytic leukemia. It is incorporated into the standard initial treatment of nearly all of these diseases. Novel anti-CD20 antibodies are currently under development...
May 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28503927/infectious-complications-in-chronic-lymphocytic-leukemia-a-retrospective-analysis-single-institution-experience
#12
L Demitrovicova, E Mikuskova, I Oravcova, S Cingelova, L Drgona, B Mladosievicova
The aim of this study was to evaluate the incidence of a variety of infectious complications in patients with CLL regarding the duration of CLL and the type of treatment. We present the retrospective analysis of patients with CLL treated at our institution in years 2004-2016. We collected data about the type of infection, pathogenes, treatment and severity of infections surpassed in connection with administration treatment. In the study one hundred and ten patients were evaluated. The average age of patients was 61...
2017: Neoplasma
https://www.readbyqxmd.com/read/28499646/dancing-partners-at-the-ball-rational-selection-of-next-generation-anti-cd20-antibodies-for-combination-therapy-of-chronic-lymphocytic-leukemia-in-the-novel-agents-era
#13
REVIEW
L A Butler, C S Tam, J F Seymour
The anti-CD20 antibodies represent a major advancement in the therapeutic options available for chronic lymphocytic leukemia. The addition of rituximab, ofatumumab and obinutuzumab to various chemotherapy regimens has led to considerable improvements in both response and survival. Ocaratuzumab, veltuzumab and ublituximab are currently being explored within the trial setting. We review the current status of these antibodies, and discuss how their mechanisms of action may impact on the choice of combinations with novel small molecule agents...
May 3, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28487504/obinutuzumab-is-effective-in-chronic-lymphocytic-leukemia-and-rheumatoid-arthritis-after-rituximab-failure-a-case-report
#14
Curtis Lachowiez, Atul Deodhar, Eliana Kozin, Stephen Spurgeon
BACKGROUND Chronic lymphocytic leukemia (CLL) is the most common leukemia affecting older adults. As such, many of these patients suffer from co-existing disease states, and the provider must take these comorbidities into account when determining a treatment regimen. The widespread use of monoclonal antibodies (mAbs) has drastically changed the treatment landscape of multiple diseases, ranging from leukemia to autoimmune conditions such as rheumatoid arthritis. CASE REPORT We present the case of a patient who had progression of his CLL and rheumatoid symptoms on rituximab therapy, and was subsequently treated with the second-generation anti-CD20 antibody obinutuzumab...
May 10, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28466278/improving-antibody-based-cancer-therapeutics-through-glycan-engineering
#15
REVIEW
Xiaojie Yu, Michael J E Marshall, Mark S Cragg, Max Crispin
Antibody-based therapeutics has emerged as a major tool in cancer treatment. Guided by the superb specificity of the antibody variable domain, it allows the precise targeting of tumour markers. Recently, eliciting cellular effector functions, mediated by the Fc domain, has gained traction as a means by which to generate more potent antibody therapeutics. Extensive mutagenesis studies of the Fc protein backbone has enabled the generation of Fc variants that more optimally engage the Fcγ receptors known to mediate cellular effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and cellular phagocytosis...
May 2, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28435325/the-clinical-development-of-obinutuzumab-for-the-treatment-of-follicular-lymphoma
#16
REVIEW
Barbara Ma, Chaitra Ujjani
Impressive progress has been made in recent decades for advanced-stage follicular lymphoma with the availability of anti-CD20 monoclonal antibodies, initially rituximab and more recently obinutuzumab. Obinutuzumab is a unique, third-generation, fully humanized glycoengineered IgG1 type II anti-CD20 monoclonal antibody. It has been shown to have increased antitumor activity compared to rituximab in preclinical studies, including whole-blood B-cell depletion assays, xenograft models, and primate models. This has spurred on the development of obinutuzumab through Phase I/II trials as monotherapy and in combination with chemotherapeutic agents and other targeted therapies...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28407142/obinutuzumab-induces-superior-b-cell-cytotoxicity-to-rituximab-in-rheumatoid-arthritis-and-systemic-lupus-erythematosus-patient-samples
#17
Venkat Reddy, Christian Klein, David A Isenberg, Martin J Glennie, Geraldine Cambridge, Mark S Cragg, Maria J Leandro
Objective.: A proportion of RA and SLE patients treated with standard doses of rituximab (RTX) display inefficient B cell deletion and poor clinical responses that can be augmented by delivering higher doses, indicating that standard-dose RTX is a sub-optimal therapy in these patients. This study aimed to investigate whether better responses could be achieved with mechanistically different anti-CD20 mAbs. Methods.: We compared RTX with obinutuzumab (OBZ), a new-generation, glycoengineered type II anti-CD20 mAb, in a series of in vitro assays measuring B cell cytotoxicity in RA and SLE patient samples...
April 11, 2017: Rheumatology
https://www.readbyqxmd.com/read/28405525/obinutuzumab-mediated-high-affinity-ligation-of-fc%C3%AE-riiia-cd16-primes-nk-cells-for-ifn%C3%AE-production
#18
Cristina Capuano, Chiara Pighi, Rosa Molfetta, Rossella Paolini, Simone Battella, Gabriella Palmieri, Giuseppe Giannini, Francesca Belardinilli, Angela Santoni, Ricciarda Galandrini
Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC), based on the recognition of IgG-opsonized targets by the low-affinity receptor for IgG FcγRIIIA/CD16, represents one of the main mechanisms by which therapeutic antibodies (mAbs) mediate their antitumor effects. Besides ADCC, CD16 ligation also results in cytokine production, in particular, NK-derived IFNγ is endowed with a well-recognized role in the shaping of adaptive immune responses. Obinutuzumab is a glycoengineered anti-CD20 mAb with a modified crystallizable fragment (Fc) domain designed to increase the affinity for CD16 and consequently the killing of mAb-opsonized targets...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28375786/differences-in-treatment-effect-size-between-overall-survival-and-progression-free-survival-in-immunotherapy-trials-a-meta-epidemiologic-study-of-trials-with-results-posted-at-clinicaltrials-gov
#19
Aidan Tan, Raphael Porcher, Perrine Crequit, Philippe Ravaud, Agnes Dechartres
Purpose We aimed to compare treatment effect sizes between overall survival (OS) and progression-free survival (PFS) in trials of US Food and Drug Administration-approved oncology immunotherapy drugs with results posted at ClinicalTrials.gov . Methods We searched ClinicalTrials.gov for phase II to IV cancer trials of Food and Drug Administration-approved immunotherapy drugs and selected those reporting results for both OS and PFS. For each trial, we extracted the hazard ratios (HRs) with 95% CIs for both outcomes and evaluated the differences by a ratio of HRs (rHRs): the HR for PFS to that for OS...
May 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28342061/cost-effectiveness-analysis-of-obinutuzumab-for-previously-untreated-chronic-lymphocytic-leukaemia-in-portuguese-patients-who-are-unsuitable-for-full-dose-fludarabine-based-therapy
#20
Ana Teresa Paquete, Luís Silva Miguel, Ursula Becker, Catarina Pereira, Carlos Gouveia Pinto
BACKGROUND: Chronic lymphocytic leukaemia (CLL) mostly affects patients with comorbidities and limited therapeutic options. Obinutuzumab in combination with chlorambucil (GClb) is a new therapeutic option for previously untreated CLL patients who are unsuitable for full-dose fludarabine-based therapy. This combination delays disease progression but incurs additional costs; thus, an assessment of its value for money is relevant. OBJECTIVE: To estimate the incremental cost-utility ratio of GClb in comparison with (i) rituximab in combination with chlorambucil (RClb), and (ii) chlorambucil alone (Clb) from the perspective of the Portuguese National Health Service (NHS)...
March 24, 2017: Applied Health Economics and Health Policy
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