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https://www.readbyqxmd.com/read/28213687/ofatumumab-for-the-treatment-of-childhood-nephrotic-syndrome
#1
Chia-Shi Wang, Rochelle Schmidt Liverman, Rouba Garro, Roshan Punnoose George, Anastacia Glumova, Alana Karp, Stephanie Jernigan, Barry Warshaw
BACKGROUND: Ofatumumab is a humanized anti-CD20 monoclonal antibody that has recently garnered interest as a potential therapeutic agent for nephrotic syndrome. We report our center's experience in administering ofatumumab to five pediatric patients with idiopathic nephrotic syndrome. METHODS: Between March 2015 and November 2016, five patients were treated with ofatumumab. One patient had post-transplant recurrent focal segmental glomerulosclerosis (FSGS) which had been resistant to plasmapheresis and numerous immunosuppressive agents...
February 17, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28205194/novel-and-expanded-oncology-drug-approvals-of-2016-part-2-new-options-in-the-management-of-hematologic-malignancies
#2
REVIEW
Todd C Knepper, James Saller, Christine M Walko
The recent past has brought pharmacotherapeutic advances that benefit patients with hematologic malignancies. In 2016, two novel hematology drugs were approved and four previously approved hematology drugs were granted expanded use for the treatment of appropriate patient populations by the US Food and Drug Administration. These new approvals and indications represent significant steps forward in patient management: they include the first-in-class B-cell lymphoma 2 inhibitor, venetoclax, the newest targeted therapy available for the treatment of hematologic malignancies; and nivolumab, the first immune checkpoint inhibitor to be approved for treatment of a hematologic malignancy...
February 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28185174/current-treatment-of-chronic-lymphocytic-leukemia
#3
REVIEW
Krzysztof Jamroziak, Bartosz Puła, Jan Walewski
A number of new treatment options have recently emerged for chronic lymphocytic leukemia (CLL) patients, including the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, phosphatidylinositol-3-kinase (PI3K) delta isoform inhibitor idelalisib combined with rituximab, the Bcl-2 antagonist venetoclax, and the new anti-CD20 antibodies obinutuzumab and ofatumumab. Most of these agents are already included into treatment algorithms defined by international practice guidelines, but more clinical investigations are needed to answer still remaining questions...
January 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28140725/complement-dependent-cytotoxicity-induced-by-therapeutic-antibodies-in-b-cell-acute-lymphoblastic-leukemia-is-dictated-by-target-antigen-expression-levels-and-augmented-by-loss-of-membrane-bound-complement-inhibitors
#4
Floris C Loeff, H M Esther van Egmond, Bart A Nijmeijer, J H Frederik Falkenburg, Constantijn J Halkes, Inge Jedema
To optimally utilize therapeutic monoclonal antibodies in the treatment of B-cell acute lymphoblastic leukemia (B-ALL) understanding their mechanisms of action and the factors influencing these mechanisms is required. We show strong correlations between target antigen expression levels and sensitivity to complement-dependent cytotoxicity (CDC) induced by rituximab, ofatumumab, or alemtuzumab in a panel of cell lines derived from primary B-ALL cells and in primary B-ALL samples. Simultaneous loss of expression of membrane-bound complement regulatory proteins (mCRP) CD55 and CD59 due to glycophosphatidylinositol-anchor deficiency, significantly increased sensitivity to CDC...
January 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28126927/efficacy-and-safety-of-dinaciclib-versus-ofatumumab-in-patients-with-relapsed-refractory-chronic-lymphocytic-leukemia
#5
Paolo Ghia, Lydia Scarfò, Susan Perez, Kumudu Pathiraja, Martha Derosier, Karen Small, Christine McCrary Sisk, Nigel Patton
No abstract text is available yet for this article.
January 26, 2017: Blood
https://www.readbyqxmd.com/read/28105602/ibrutinib-a-review-in-chronic-lymphocytic-leukaemia
#6
Emma D Deeks
Ibrutinib (Imbruvica(®)) is an oral irreversible inhibitor of Bruton's tyrosine kinase, a B-cell receptor (BCR) signalling kinase expressed by various haematopoietic cells, B-cell lymphomas and leukaemias. The drug is indicated for the treatment of certain haematological malignancies, including chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), which are the focus of this review. In phase III CLL/SLL trials, ibrutinib monotherapy was more effective than chlorambucil in the first-line treatment of elderly patients (RESONATE-2) and more effective than ofatumumab in previously-treated adults (RESONATE)...
February 2017: Drugs
https://www.readbyqxmd.com/read/28096698/burkitt-lymphoma-in-adolescents-and-young-adults-management-challenges
#7
REVIEW
Massimo Dozzo, Francesca Carobolante, Pietro Maria Donisi, Annamaria Scattolin, Elena Maino, Rosaria Sancetta, Piera Viero, Renato Bassan
About one-half of all Burkitt lymphoma (BL) patients are younger than 40 years, and one-third belong to the adolescent and young adult (AYA) subset, defined by an age between 15 and 25-40 years, based on selection criteria used in different reports. BL is an aggressive B-cell neoplasm displaying highly characteristic clinico-diagnostic features, the biologic hallmark of which is a translocation involving immunoglobulin and c-MYC genes. It presents as sporadic, endemic, or epidemic disease. Endemicity is pathogenetically linked to an imbalance of the immune system which occurs in African children infected by malaria parasites and Epstein-Barr virus, while the epidemic form strictly follows the pattern of infection by HIV...
2017: Adolescent Health, Medicine and Therapeutics
https://www.readbyqxmd.com/read/28062113/indirect-treatment-comparisons-of-ibrutinib-versus-physician-s-choice-and-idelalisib-plus-ofatumumab-in-patients-with-previously-treated-chronic-lymphocytic-leukemia
#8
REVIEW
Sonja Sorensen, Mark Wildgust, Nishan Sengupta, Cristina Trambitas, Joris Diels, Suzy van Sanden, Yingxin Xu, Emily Dorman
PURPOSE: Treatment options for patients with relapsed or refractory chronic lymphocytic leukemia (R/R CLL) are limited. Until recently, few effective treatment options existed, and even with the advent of new agents, studies evaluating comparative efficacy are scarce. In the Ibrutinib Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (RESONATE) Phase III study, ibrutinib, an oral, once-a-day, first-in-class covalent Bruton tyrosine kinase inhibitor, improved progression-free survival (PFS) and overall survival (OS) compared with ofatumumab (PFS hazard ratio [HR] = 0...
January 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28043164/current-treatment-options-and-investigational-drugs-for-waldenstrom-s-macroglobulinemia
#9
Maria Gavriatopoulou, Evangelos Terpos, Efstathios Kastritis, Meletios A Dimopoulos
Waldenström's Macroglobulinemia (WM) is a rare, indolent, incurable, low-grade B-cell lymphoplasmacytic neoplasm. This review article provides a modern clinical perspective of the individualized management of patients with symptomatic WM, in the context of the updated treatment guidelines and the currently available trial data. Areas covered: Rituximab-based regimens (such as the dexamethasone, rituximab and cyclophosphamide combination, DRC) are the most widely used in the management of both newly diagnosed and relapsed/refractory patients with WM...
January 3, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28041583/combination-of-ofatumumab-and-reduced-dose-chop-for-diffuse-large-b-cell-lymphomas-in-patients-aged-80-years-or-older-an-open-label-multicentre-single-arm-phase-2-trial-from-the-lysa-group
#10
Frédéric Peyrade, Serge Bologna, Vincent Delwail, Jean François Emile, Laurent Pascal, Christophe Fermé, Jean-Marc Schiano, Bertrand Coiffier, Bernadette Corront, Hassan Farhat, Christophe Fruchart, Herve Ghesquieres, Margaret Macro, Hervé Tilly, Bachra Choufi, Richard Delarue, Olivier Fitoussi, Jean Gabarre, Corinne Haioun, Fabrice Jardin
BACKGROUND: In 2011 we reported a rituximab plus miniCHOP (reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone) combination for patients older than 80 years with diffuse large B-cell lymphoma (DLBCL). The 2-year overall survival was 59% (95% CI 49-67) with an excess of early toxicity. To improve those results we tested the same chemotherapy protocol in combination with ofatumumab and a pre-phase treatment. METHODS: For this open-label, multicentre, single-group, phase 2 trial, we recruited patients older than 80 years with untreated histologically-proven CD20-positive DLBCL, Ann Arbor stage I to IV, from 41 academic and hospital centres in France and Belgium...
January 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28029326/ofatumumab-versus-rituximab-salvage-chemoimmunotherapy-in-relapsed-or-refractory-diffuse-large-b-cell-lymphoma-the-orcharrd-study
#11
Gustaaf W van Imhoff, Andrew McMillan, Matthew J Matasar, John Radford, Kirit M Ardeshna, Kazimierz Kuliczkowski, WonSeog Kim, Xiaonan Hong, Jette Soenderskov Goerloev, Andrew Davies, María Dolores Caballero Barrigón, Michinori Ogura, Sirpa Leppä, Michael Fennessy, Qiming Liao, Bronno van der Holt, Steen Lisby, Anton Hagenbeek
Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients with CD20(+) DLBCL age ≥ 18 years who had experienced their first relapse or who were refractory to first-line R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like treatment were randomly assigned between three cycles of R-DHAP or O-DHAP...
December 28, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27972387/ofatumumab-as-a-combination-therapy-versus-other-treatment-regimens-in-patients-with-untreated-relapsed-or-refractory-chronic-lymphocytic-leukaemia-a-systematic-review-of-randomised-controlled-trials
#12
H R Gadi, P Patel, S Shaikh, M K Rai
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/27914971/once-weekly-ofatumumab-in-untreated-or-relapsed-waldenstr%C3%A3-m-s-macroglobulinaemia-an-open-label-single-arm-phase-2-study
#13
Richard R Furman, Herbert A Eradat, Christine G DiRienzo, Craig C Hofmeister, Suzanne R Hayman, John P Leonard, Morton Coleman, Ranjana Advani, Asher Chanan-Khan, Julie Switzky, Qiming M Liao, Damini Shah, Roxanne C Jewell, Steen Lisby, Thomas S Lin
BACKGROUND: The development of more effective and safer treatments, especially non-chemotherapeutics, is needed for patients with Waldenström's macroglobulinaemia. The aim of the study was to assess the safety and clinical activity of intravenous ofatumumab monotherapy for untreated and relapsed Waldenström's macroglobulinaemia. METHODS: We did a phase 2, open-label, single-arm study at six centres (hospitals and cancer clinics) in the USA. Patients aged at least 18 years who were diagnosed with untreated or relapsed Waldenström's macroglobulinaemia and required treatment, received up to three cycles of weekly ofatumumab for 5 weeks...
January 2017: Lancet Haematology
https://www.readbyqxmd.com/read/27914970/ofatumumab-another-way-to-target-cd20-in-waldenstr%C3%A3-m-s-macroglobulinaemia
#14
Christian Buske
No abstract text is available yet for this article.
January 2017: Lancet Haematology
https://www.readbyqxmd.com/read/27913471/sequencing-of-chronic-lymphocytic-leukemia-therapies
#15
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/27873460/sortase-a-generated-highly-potent-anti-cd20-mmae-conjugates-for-efficient-elimination-of-b-lineage-lymphomas
#16
Liqiang Pan, Wenbin Zhao, Jun Lai, Ding Ding, Qian Zhang, Xiaoyue Yang, Minmin Huang, Shijie Jin, Yingchun Xu, Su Zeng, James J Chou, Shuqing Chen
Antibody-drug conjugate (ADC) targeting antigens expressed on the surface of tumor cells are an effective approach for delivering drugs into the cells via antigen-mediated endocytosis. One of the well-known tumor antigens, the CD20 of B-lymphocyte, has long been suggested to be noninternalizing epitope, and is thus not considered a desirable target for ADCs. Here, sortase A (srtA)-mediated transpeptidation is used to specifically conjugate triple glycine-modified monomethyl auristatin E (MMAE), a highly toxic antimitotic agent, to anti-CD20 ofatumumab (OFA) equipped with a short C-terminal LPETG (5 amino acids) tag at heavy chain (HL), which generates ADCs that show extremely strong potency in killing CD20 positive cancer cells...
November 22, 2016: Small
https://www.readbyqxmd.com/read/27854102/the-next-generation-of-targeted-molecules-for-the-treatment-of-chronic-lymphocytic-leukemia
#17
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/27830957/health-related-quality-of-life-and-patient-reported-outcomes-of-ofatumumab-plus-fludarabine-and-cyclophosphamide-versus-fludarabine-and-cyclophosphamide-in-the-complement-2-trial-of-patients-with-relapsed-cll
#18
Tadeusz Robak, Krzysztof Warzocha, K Govind Babu, Yaroslav Kulyaba, Kazimierz Kuliczkowski, Kudrat Abdulkadyrov, Javier Loscertales, Iryna Kryachok, Janusz Kłoczko, Grygoriy Rekhtman, Wojciech Homenda, Jerzy Z Błoński, Astrid McKeown, Chai-Ni Chang, Vasudha Bal, Steen Lisby, Ira V Gupta, Sebastian Grosicki
Chronic lymphocytic leukemia (CLL) is an incurable disease. Quality of life during treatment and periods of subsequent remission is therefore vital. Health-related quality of life (HRQoL) was compared in relapsed CLL during and after treatment with ofatumumab combined with fludarabine and cyclophosphamide versus fludarabine and cyclophosphamide alone. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 v3 and QLQ-CLL16 were used to assess HRQoL in this open-label, phase 3 study. Improvements in prespecified domains of patient-reported outcomes (Global Health Status [GHS]/HRQoL and B symptom scores) were recorded in both treatment arms after three cycles and were sustained after 18 months of follow-up...
November 10, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27807190/type-i-cd20-antibodies-recruit-the-b-cell-receptor-for-complement-dependent-lysis-of-malignant-b-cells
#19
Patrick J Engelberts, Marleen Voorhorst, Janine Schuurman, Tom van Meerten, Joost M Bakker, Tom Vink, Wendy J M Mackus, Esther C W Breij, Stefanie Derer, Thomas Valerius, Jan G J van de Winkel, Paul W H I Parren, Frank J Beurskens
Human IgG1 type I CD20 Abs, such as rituximab and ofatumumab (OFA), efficiently induce complement-dependent cytotoxicity (CDC) of CD20(+) B cells by binding of C1 to hexamerized Fc domains. Unexpectedly, we found that type I CD20 Ab F(ab')2 fragments, as well as C1q-binding-deficient IgG mutants, retained an ability to induce CDC, albeit with lower efficiency than for whole or unmodified IgG. Experiments using human serum depleted of specific complement components demonstrated that the observed lytic activity, which we termed "accessory CDC," remained to be dependent on C1 and the classical pathway...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27793206/mog-igg-in-nmo-and-related-disorders-a-multicenter-study-of-50-patients-part-2-epidemiology-clinical-presentation-radiological-and-laboratory-features-treatment-responses-and-long-term-outcome
#20
Sven Jarius, Klemens Ruprecht, Ingo Kleiter, Nadja Borisow, Nasrin Asgari, Kalliopi Pitarokoili, Florence Pache, Oliver Stich, Lena-Alexandra Beume, Martin W Hümmert, Marius Ringelstein, Corinna Trebst, Alexander Winkelmann, Alexander Schwarz, Mathias Buttmann, Hanna Zimmermann, Joseph Kuchling, Diego Franciotta, Marco Capobianco, Eberhard Siebert, Carsten Lukas, Mirjam Korporal-Kuhnke, Jürgen Haas, Kai Fechner, Alexander U Brandt, Kathrin Schanda, Orhan Aktas, Friedemann Paul, Markus Reindl, Brigitte Wildemann
BACKGROUND: A subset of patients with neuromyelitis optica spectrum disorders (NMOSD) has been shown to be seropositive for myelin oligodendrocyte glycoprotein antibodies (MOG-IgG). OBJECTIVE: To describe the epidemiological, clinical, radiological, cerebrospinal fluid (CSF), and electrophysiological features of a large cohort of MOG-IgG-positive patients with optic neuritis (ON) and/or myelitis (n = 50) as well as attack and long-term treatment outcomes. METHODS: Retrospective multicenter study...
September 27, 2016: Journal of Neuroinflammation
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