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Huu H Huynh, Clara Roessle, Hélène Sauvageon, Alain Plé, Isabelle Madelaine, Catherine Thieblemont, Samia Mourah, Lauriane Goldwirt
BACKGROUND: Idelalisib is the first orally active selective phosphatidylinositol 3-kinase delta inhibitor approved by Food and Drug Administration and European Medicines Agency in 2014 for the treatment of several types of blood cancer. Idelalisib is widely used as a monotherapy or in combination with rituximab, bendamustine, or ofatumumab with a significant efficacy. However, idelalisib has shown increased risk of infection and a higher frequency of serious adverse events. It may be useful to determine idelalisib concentration in human plasma to adjust dose and to manage adverse effects in clinical practice...
April 2018: Therapeutic Drug Monitoring
Michael J Robertson, Christopher W Stamatkin, David Pelloso, Jill Weisenbach, Nagendra K Prasad, Ahmad R Safa
Interleukin-18 (IL-18) is an immunostimulatory cytokine that augments antibody-dependent cellular cytotoxicity mediated by human natural killer cells against antibody-coated lymphoma cells in vitro and that has antitumor activity in animal models. Ofatumumab is a CD20 monoclonal antibody with activity against human B-cell lymphomas. A phase I study of recombinant human (rh) IL-18 given with ofatumumab was undertaken in patients with CD20 lymphoma who had undergone high-dose chemotherapy and autologous peripheral blood stem cell transplantation...
March 6, 2018: Journal of Immunotherapy
R Rahmanzadeh, M S Weber, W Brück, S Navardi, M A Sahraian
For decades, B cells were ignored in multiple sclerosis (MS) pathogenesis, and the disease was always regarded as a T cell-mediated disorder. Recent evidence shows that there is an antigen-driven B-cell response in the central nervous system of patients with MS, and memory B cells/plasma cells are detectable in MS lesions. The striking efficacy of B cell-depleting therapies in reducing the inflammatory activity of the disease highlights that B cells may play more pathogenetic roles than expected. B cells express several unique characteristic markers on their surface, for example, CD19, CD20 molecules, that provide selective targets for monoclonal antibodies...
March 7, 2018: Acta Neurologica Scandinavica
Aurélie Cabannes-Hamy, Frederic Peyrade, Fabrice Jardin, Jean-François Emile, Vincent Delwail, Nicolas Mounier, Corinne Haioun, Aurore Perrot, Olivier Fitoussi, Diane Lara, Richard Delarue, Marc André, Fritz Offner, Hervé Ghesquières, Laurent Pascal, Carole Soussain, Julien Lazarovici, Jean-Marc Schiano, Philippe Gaulard, Hervé Tilly, Catherine Thieblemont
CNS relapse is reported in 2-5% of diffuse large B-cell lymphoma (DLBCL) patients, dramatically decreasing overall survival (OS). Very few studies address incidence and risk factors of CNS relapse in very elderly patients, a challenging population to treat given their commonly associated comorbidities. A retrospective analysis was performed of 270 DLBCL patients >80 years treated between 2004 and 2013 in two multicentre phase II LYSA trials (LNH03-7B, LNH09-7B) evaluating the addition of rituximab or ofatumumab to mini-CHOP as front-line therapy...
February 23, 2018: Cancer Medicine
Paula Cramer, Julia von Tresckow, Jasmin Bahlo, Anja Engelke, Petra Langerbeins, Anna-Maria Fink, Kirsten Fischer, Clemens-Martin Wendtner, Karl-Anton Kreuzer, Stephan Stilgenbauer, Sebastian Böttcher, Barbara Eichhorst, Michael Hallek
AIM: Four Phase II trials (Clinical Trials numbers: NCT02345863, NCT02401503, NCT02445131 and NCT02689141) evaluate a different combination of targeted agents in an all-comer population of approximately 60 patients with chronic lymphocytic leukemia irrespective of prior treatment, physical fitness and genetic risk factors. Patients with a higher tumor load start with a debulking treatment with bendamustine. The subsequent induction and maintenance treatment with an anti-CD20 antibody (obinutuzumab or ofatumumab) and a targeted oral agent (ibrutinib, idelalisib or venetoclax) are continued until achievement of a complete response and minimal residual disease negativity...
February 21, 2018: Future Oncology
F Speth, C Hinze, R Häfner
No abstract text is available yet for this article.
January 1, 2018: Lupus
Alice Bonanni, Marta Calatroni, Matteo D'Alessandro, Sara Signa, Enrica Bertelli, Michela Cioni, Eddi Di Marco, Roberto Biassoni, Gianluca Caridi, Giulia Ingrasciotta, Roberta Bertelli, Armando Di Donato, Maurizio Bruschi, Alberto Canepa, Giorgio Piaggio, Pietro Ravani, Gian Marco Ghiggeri
AIMS: Anti-CD20 antibodies are increasingly being used to treat idiopathic nephrotic syndrome (INS) in children. While they may allow steroid and calcineurin-inhibitor withdrawal, repeated infusions of anti-CD20 antibodies are often required to maintain remission. Data on their potential toxicity in INS are needed to consider repeated infusions. METHODS: We reported data on side effects related to the use of rituximab (a chimeric anti-body; 130 pts) and ofatumumab (a humanized anti-body; 37 pts) in children with INS (steroid-dependent and steroid/calcineurin-inhibitor dependent disease) treated in a national referral center during a 9-year period (400 treatments; follow-up 1-9 years)...
February 13, 2018: British Journal of Clinical Pharmacology
Jason T Yoon, Mark S Longtine, Bernadette V Marquez-Nostra, Richard L Wahl
Radioimmunotherapies with monoclonal antibodies (mAbs) to the B-lymphocyte antigen 20 (CD20) are effective treatments for B-cell lymphomas, but United States Food and Drug Administration (FDA)-approved radioimmunotherapies exclusively use radiolabeled murine antibodies, potentially limiting re-dosing. The FDA recently approved two unlabeled anti-CD20 monoclonal antibodies, obinutizumab and ofatumumab, termed "next generation" as they are humanized (obinituzumab) or fully human (ofatumumab), thus potentially allowing a greater potential for re-dosing than with previous generation anti-CD20 antibodies, including rituximab (chimeric) and tositumumab (murine) which contain more murine peptide sequences...
January 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Maeve P Crowley, Vickie McDonald, Marie Scully
No abstract text is available yet for this article.
January 4, 2018: New England Journal of Medicine
Mehmet S Copur, Curtis Gnewuch, Megan Schriner, Mark Tharnish, Mithat Gonen, Monica McDonald, Jami Kezeor, Ryan C Ramaekers, Dron Gauchan, Douglas Clark, Lois Greenwalt, Mary Mickey, Max Norvell
Purpose Increasing new cancer cases and approval of effective but expensive new drugs extending survival have led to unsustainable cancer care costs. Potential cost savings by a hypothetical dose down-rounding project of monoclonal antibodies at a community-based cancer center is presented. Methods From October 2014 through October 2015, metastatic cancer patients receiving monoclonal antibodies at CHI-Health St Francis Cancer Treatment Center in Grand Island, Nebraska, were identified through electronic health records...
January 1, 2017: Journal of Oncology Pharmacy Practice
Jennifer R Brown, Florence Cymbalista, Jeff Sharman, Ira Jacobs, Pilar Nava-Parada, Anthony Mato
Chronic lymphocytic leukemia (CLL) is managed with observation for asymptomatic or clinically silent disease; pharmacologic intervention is generally required for symptomatic patients with clinically significant adenopathy or cytopenia. In the front-line treatment of CLL, the current standard-of-care includes chemotherapy in combination with an anti-CD20 monoclonal antibody (e.g., rituximab, ofatumumab, or obinutuzumab) or ibrutinib as single agent. Despite the evolving treatment paradigm toward targeted therapy, it is likely that rituximab (plus chemotherapy), with or without targeted agents, will retain a significant role in CLL treatment...
December 6, 2017: Oncologist
Nicoletta Mancianti, Giulio Monaci, Fabio Rollo, Paola Buracchi, Andrea Guarnieri, Marina Di Luca, Mauro Martello, Guido Garosi
Modern methods for desensitization protocol rely heavily on combined apheresis therapy and Rituximab, a chimeric (murine and human) anti-CD20 antibody used in AB0 incompatible kidney transplants. Severe infusion related reactions due to the administration of Rituximab are reported in 10% of patients. These adverse reactions may hinder the completion of the desensitization protocol. Therefore, it's useful to test alternative B cell depleting therapies. Our clinical case focuses on a 41-year-old male who developed an adverse infusion reaction following the administration of Rituximab and was given Ofatumumab as an alternative treatment...
December 5, 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
Fanny Huynh Du, Elizabeth A Mills, Yang Mao-Draayer
The clinical success of anti-CD20 monoclonal antibody (mAb)-mediated B cell depletion therapy has contributed to the understanding of B cells as major players in several autoimmune diseases. The first therapeutic anti-CD20 mAb, rituximab, is a murine-human chimera to which many patients develop antibodies and/or experience infusion-related reactions. A second generation of anti-CD20 mAbs has been designed to be more effective, better tolerated, and of lower immunogenicity. These include the humanized versions: ocrelizumab, obinutuzumab, and veltuzumab, and the fully human, ofatumumab...
November 16, 2017: Auto- Immunity Highlights
Idanna Innocenti, Francesco Autore, Raffaella Pasquale, Francesca Morelli, Dimitar G Efremov, Luca Laurenti
Elderly patients with chronic lymphocytic leukemia (CLL) or patients with comorbidities are often treated with chlorambucil (Chl) as front-line therapy despite relatively low response rates. The addition of a monoclonal anti-CD20 antibody to Chl substantially increases response rates and prolongs progression-free survival (PFS) in these patients, without increasing toxicity. As a result, the ESMO guidelines recommend that previously untreated CLL patients with relevant co-morbidity, but without TP53 deletion/mutation, should be treated with the combination of Chl plus an anti-CD20 antibody (rituximab, ofatumumab or obinutuzumab)...
December 2017: Expert Review of Hematology
Troy Z Horvat, Amanda N Seddon, Adebayo Ogunniyi, Amber C King, Larry W Buie, Ryan J Daley
OBJECTIVE: To review the pharmacology, efficacy, and safety of Food and Drug Administration approved and promising immunotherapy agents used in the treatment of acute lymphoblastic leukemia (ALL). DATA SOURCES: A literature search was performed of PubMed and MEDLINE databases (1950 to July 2017) and of abstracts from the American Society of Hematology and the American Society of Clinical Oncology. Searches were performed utilizing the following key terms: rituximab, blinatumomab, inotuzumab, ofatumumab, obinutuzumab, Blincyto, Rituxan, Gazyva, Arzerra, CAR T-cell, and chimeric antigen receptor (CAR)...
October 1, 2017: Annals of Pharmacotherapy
Zahra Payandeh, Masoumeh Rajabibazl, Yousef Mortazavi, Azam Rahimpour, Amir Hossein Taromchi
Background: Ofatumumab, an anti-CD20 mAb, was approved in 2009 for the treatment of chronic lymphocytic leukemia. This mAb acts through immune-mediated mechanisms, in particular complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity by natural killer cells as well as antibody-dependent phagocytosis by macrophages. Apoptosis induction is another mechanism of this antibody. Computational docking is the method of predicting the conformation of an antibody-antigen from its separated elements...
October 10, 2017: Iranian Biomedical Journal
Gilles Salles, Martin Barrett, Robin Foà, Joerg Maurer, Susan O'Brien, Nancy Valente, Michael Wenger, David G Maloney
Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma...
October 2017: Advances in Therapy
Gaetano La Manna, Olga Baraldi, Vania Cunia, Valeria Corradetti, Valeria Aiello, Marco Busutti, Lorenzo Gasperoni, Alessandra Spazzoli, Giorgia Comai
The membranous nephropathy (MN) is the major cause of nephrotic syndrome in in the adult, account for 20% of cases with annual incidence is 1 in 100.000. In the past 10 years, the role of podocytes has been identified; environmental triggers in genetically predisposed patients can activate podocytes to exhibit antigenic epitopes (receptor of phospholipase A2, thrombospondin type 1) that become targets of specific autoantibodies with subsequent complement activation. The discovery of this mechanisms has opened new horizons in the therapy of MN and novel drugs are available with more specific mechanism of action...
September 28, 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
A Wolfromm, R Delarue
Emergence of new molecules has considerably reshaped the management of patients in onco-hematology. Cytotoxic chemotherapy has not been altered, and CHOP remains the reference treatment for lymphomas. However, the development of targeted therapies has allowed for a broader spectrum of treatments. Immunotherapy with monoclonal antibodies entered the market with rituximab in diffuse large B-cell lymphomas, in the 1990s and it is now developing as new-generation anti-CD20 antibodies (obinotuzumab and ofatumumab)...
October 2017: La Revue de Médecine Interne
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...
December 2017: Clinical Lymphoma, Myeloma & Leukemia
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