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https://www.readbyqxmd.com/read/28516439/reassessment-of-anti-cd20-therapy-in-lymphoid-malignancies-impact-limitations-and-new-directions
#1
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/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
#2
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/28456094/new-biologics-in-the-treatment-of-rare-glomerular-diseases-of-childhood
#3
REVIEW
Paolo Cravedi, Andrea Angeletti, Giuseppe Remuzzi
Minimal change disease and focal segmental glomerulosclerosis are rare but important causes of end-stage kidney disease in children. Though their pathogenesis is still unclear, evidence of immune abnormalities provided the background for the use of immunosuppressive drugs, such as corticosteroids, calcineurin inhibitors, antiproliferative and alkylating agents. Unfortunately, these treatments fail to achieve a sustained remission in a significant portion of patients and are burdened by significant toxicities...
April 26, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28450895/targeting-b-cells-in-relapsing-remitting-multiple-sclerosis-from-pathophysiology-to-optimal-clinical-management
#4
REVIEW
Stefan Bittner, Tobias Ruck, Heinz Wiendl, Oliver M Grauer, Sven G Meuth
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease that is caused by an autoimmune response against central nervous system (CNS) structures. Traditionally considered a T-cell-mediated disorder, the contribution of B cells to the pathogenesis of MS has long been debated. Based on recent promising clinical results from CD20-depleting strategies by three therapeutic monoclonal antibodies in clinical phase II and III trials (rituximab, ocrelizumab and ofatumumab), targeting B cells in MS is currently attracting growing interest among basic researchers and clinicians...
January 2017: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/28439883/an-update-for-richter-syndrome-new-directions-and-developments
#5
REVIEW
Toby A Eyre, Anna Schuh
High-grade transformation of chronic lymphocytic leukaemia [Richter syndrome (RS)] is rare and represents a unique and uncommon clinical challenge. Clonally related diffuse large B cell type RS is a chemotherapy-resistant and devastating disease. Patients are typically elderly, immunosuppressed and present with a rapidly deteriorating performance status. Historical outcomes suggest a median overall survival of approximately 8 months. RS remains is an area of high unmet clinical need. The molecular profile and treatment needs of patients are likely to change over time with the advent of novel B cell receptor inhibitors, monoclonal antibodies and BH3 mimetics...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28421390/ofatumumab-combined-with-chlorambucil-for-previously-untreated-chronic-lymphocytic-leukemia-a-phase-i-ii-open-label-study-in-japan
#6
Kiyohiko Hatake, Michinori Ogura, Kohichi Takada, Masafumi Taniwaki, Fanghong Zhang, Taizo Fujita, Kiyoshi Ando
Elderly/comorbid patients with chronic lymphocytic leukemia (CLL) require low-toxicity treatments. Internationally, the standard treatment for such patients is chlorambucil and an anti-CD20 therapy; however, chlorambucil is not approved in Japan. The aim of the present study was to evaluate the safety, efficacy and pharmacokinetics of ofatumumab in combination with chlorambucil in Japanese patients with previously untreated CLL who were inappropriate for fludarabine-based therapy. Ten patients were enrolled and treated in this study, all of whom received at least one dose of the study drugs...
April 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28314744/randomised-controlled-trial-comparing-ofatumumab-to-rituximab-in-children-with-steroid-dependent-and-calcineurin-inhibitor-dependent-idiopathic-nephrotic-syndrome-study-protocol
#7
Pietro Ravani, Alice Bonanni, Gian Marco Ghiggeri
INTRODUCTION: Oral steroids induce remission in about 90% of children with idiopathic nephrotic syndrome (INS), which is characterised by severe proteinuria and hypoalbuminaemia. Some children become steroid-dependent (SD) and require addition of calcineurin inhibitors (CNI) to maintain remission. Since these oral agents are toxic, alternative interventions are needed for long-term treatment. The anti-CD20 antibody rituximab has shown promising steroid-sparing properties in clinical trials, but benefits are less convincing in complicated forms of SD-INS...
March 17, 2017: BMJ Open
https://www.readbyqxmd.com/read/28273193/-drug-therapy-of-lymphomas
#8
Lajos Gergely
The therapy of lymphomas has undergone a major expansion during the last decade. Novel therapeutic targets have appeared beyond classical chemotherapeutic combinations. These novel drugs have very pronounced action across lymphoma types, and their toxicity profile is usually better tolerable compared to standard chemotherapies. These new therapies are enabling us to offer treatment to those patients who have refractory disease, and we had no option to treat them before these drugs. The author describes several new therapeutic options...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28269762/cloning-and-molecular-characterization-of-the-cdnas-encoding-the-variable-regions-of-an-anti-cd20-monoclonal-antibody
#9
Dariush Shanehbandi, Jafar Majidi, Tohid Kazemi, Behzad Baradaran, Leili Aghebati-Maleki
BACKGROUND: CD20-based targeting of B-cells in hematologic malignancies and autoimmune disorders is associated with outstanding clinical outcomes. Isolation and characterization of VH and VL cDNAs encoding the variable regions of the heavy and light chains of monoclonal antibodies (MAb) is necessary to produce next generation MAbs and their derivatives such as and bispecific antibodies (bsAb) and single-chain variable fragments (scFv). OBJECTIVE: This study was aimed at cloning and characterization of the VH and VL cDNAs from a hybridoma cell against the CD20 antigen...
February 24, 2017: Human Antibodies
https://www.readbyqxmd.com/read/28257752/efficacy-and-safety-of-idelalisib-in-combination-with-ofatumumab-for-previously-treated-chronic-lymphocytic-leukaemia-an-open-label-randomised-phase-3-trial
#10
Jeffrey A Jones, Tadeusz Robak, Jennifer R Brown, Farrukh T Awan, Xavier Badoux, Steven Coutre, Javier Loscertales, Kerry Taylor, Elisabeth Vandenberghe, Malgorzata Wach, Nina Wagner-Johnston, Loic Ysebaert, Lyndah Dreiling, Ronald Dubowy, Guan Xing, Ian W Flinn, Carolyn Owen
BACKGROUND: Idelalisib, a selective inhibitor of PI3Kδ, is approved for the treatment of patients with relapsed chronic lymphocytic leukaemia (CLL) in combination with rituximab. We aimed to assess the efficacy and safety of idelalisib in combination with a second-generation anti-CD20 antibody, ofatumumab, in a similar patient population. METHODS: In this global, open-label, randomised, controlled phase 3 trial, we enrolled patients with relapsed CLL progressing less than 24 months from last therapy...
March 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28236475/update-of-the-grupo-espa%C3%A3-ol-de-leucemia-linfoc%C3%A3-tica-cr%C3%A3-nica-clinical-guidelines-of-the-management-of-chronic-lymphocytic-leukemia
#11
José A García-Marco, Julio Delgado, José A Hernández-Rivas, Ángel Ramírez Payer, Javier Loscertales Pueyo, Isidro Jarque, Pau Abrisqueta, Pilar Giraldo, Rafael Martínez, Lucrecia Yáñez, Mª José Terol, Marcos González, Francesc Bosch
BACKGROUND AND OBJECTIVE: The broad therapeutic arsenal and the biological heterogeneity of patients with chronic lymphocytic leukemia (CLL) makes it difficult to standardize treatment for CLL patients with specific clinical settings in routine clinical practice. These considerations prompted us to elaborate the present consensus document, which constitutes an update of the previous version published in 2013, mainly focusing on novel treatment strategies that have been developed over last 5 years, namely B-cell receptor inhibitors (ibrutinib and idelalisib), anti-CD20 monoclonal antibodies (ofatumumab and obinutuzumab), and Bcl-2 inhibitors (venetoclax)...
April 21, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28213687/ofatumumab-for-the-treatment-of-childhood-nephrotic-syndrome
#12
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...
May 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
#13
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
#14
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
#15
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
#16
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
#17
REVIEW
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
#18
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
#19
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
#20
REVIEW
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...
February 2017: Expert Opinion on Investigational Drugs
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