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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
#1
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...
November 30, 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27914970/ofatumumab-another-way-to-target-cd20-in-waldenstr%C3%A3-m-s-macroglobulinaemia
#2
Christian Buske
No abstract text is available yet for this article.
November 30, 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27913471/sequencing-of-chronic-lymphocytic-leukemia-therapies
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/27742065/current-strategies-to-create-tailored-and-risk-adapted-therapies-for-cll-patients
#9
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/27731748/ofatumumab-plus-fludarabine-and-cyclophosphamide-in-relapsed-chronic-lymphocytic-leukemia-results-from-the-complement-2-trial
#10
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, Michele M Gorczyca, Jodi L Carey, Chai-Ni Chang, Steen Lisby, Ira V Gupta, Sebastian Grosicki
: In this multicenter, open-label, phase III study, patients with relapsed chronic lymphocytic leukemia (CLL) were randomized (1:1) to receive ofatumumab plus fludarabine and cyclophosphamide (OFA + FC) or FC alone; the primary endpoint being progression-free survival (PFS) assessed by an independent review committee (IRC). Between March 2009 and January 2012, 365 patients were randomized (OFA + FC: n = 183; FC: n = 182). Median IRC-assessed PFS was 28.9 months with OFA + FC versus 18...
October 12, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27724158/phase-2-study-of-ofatumumab-fludarabine-and-cyclophosphamide-in-relapsed-refractory-waldenstr%C3%A3-m-s-macroglobulinemia
#11
Maria Gavriatopoulou, Efstathios Kastritis, Marie-Christine Kyrtsonis, Theodoros P Vassilakopoulos, Maria Roussou, Despoina Fotiou, Magdalini Migkou, Maria Mpakiri, Anna Tasidou, Evangelos Terpos, Meletios Athanasios Dimopoulos
No abstract text is available yet for this article.
October 10, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27718747/anti-cd20-monoclonal-antibodies-in-multiple-sclerosis
#12
Irene Del Pilar Moreno Torres, Antonio García-Merino
INTRODUCTION: The therapeutic utility of the anti-CD20 monoclonal antibodies (mAbs) is currently being evaluated in multiple sclerosis (MS) in line with the better understanding of the role of B lymphocytes in MS pathogenesis. AREA COVERED: We conducted a literature search using Medline/Pub Med database of basic research and available controlled trials about anti-CD20 mAbs in MS. Additionally, ongoing studies were identified in the ClinicalTrials.gov database. B cells exert multiple inflammatory and regulatory functions playing an important role in MS pathogenesis as is demonstrated by the production of autoantibodies, infiltration of B cells in MS lesions and the formation of ectopic B cell follicle-like structures in meninges, among others...
October 10, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27687621/ofatumumab-in-two-pediatric-nephrotic-syndrome-patients-allergic-to-rituximab
#13
Marina Vivarelli, Manuela Colucci, Alice Bonanni, Martina Verzani, Jessica Serafinelli, Francesco Emma, Gianmarco Ghiggeri
BACKGROUND: Rituximab, a chimeric anti-CD20 monoclonal antibody, is an effective treatment in steroid-dependent nephrotic syndrome (SDNS). However, some patients develop adverse reactions. CASE-DIAGNOSIS/TREATMENT: Patient 1, a 14-year-old boy with SDNS since the age of 2, was treated with oral prednisone, cyclosporine A (CsA) and mycophenolate mofetil. A first infusion of rituximab at age 12 years was well tolerated, but this was followed by a prolonged relapse unresponsive to oral prednisone, mycophenolate mofetil and CsA...
September 29, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/27645620/chemotherapy-plus-ofatumumab-at-standard-or-mega-dose-in-relapsed-cll-cosmic-trial-study-protocol-for-a-phase-ii-randomised-controlled-trial
#14
Dena R Howard, Talha Munir, Anna Hockaday, Andy C Rawstron, Laura Collett, Jamie B Oughton, David Allsup, Adrian Bloor, David Phillips, Peter Hillmen
BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia. Combination immunochemotherapy such as fludarabine, cyclophosphamide and rituximab is the standard first line therapy in fit patients, but there is limited evidence regarding the optimal treatment of patients after relapse. Ofatumumab as monotherapy has been proven to be effective in the treatment of relapsed, refractory CLL, and as it is not myelotoxic, it is an ideal drug to combine with chemotherapy...
2016: Trials
https://www.readbyqxmd.com/read/27570087/ofatumumab-monotherapy-as-a-consolidation-strategy-in-patients-with-previously-untreated-chronic-lymphocytic-leukaemia-a-phase-2-trial
#15
Paolo Strati, Mark Lanasa, Timothy G Call, Jose F Leis, Danielle M Brander, Betsy R LaPlant, Adam M Pettinger, Wei Ding, Sameer A Parikh, Curtis A Hanson, Asher A Chanan-Khan, Deborah A Bowen, Michael Conte, Neil E Kay, Tait D Shanafelt
BACKGROUND: Although several consolidation strategies to prolong treatment-free survival (TFS) in chronic lymphocytic leukaemia have been investigated, most have proven either ineffective or toxic. Ofatumumab is a human type I anti-CD20 antibody approved by the US Food and Drug Administration as maintenance treatment of patients with recurrent or progressive chronic lymphocytic leukaemia who are in complete or partial response after at least two lines of treatment; higher efficacy might be observed if used as consolidation strategy than without consolidation in previously untreated patients...
September 2016: Lancet Haematology
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
#16
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/27521873/new-monoclonal-antibodies-for-the-treatment-of-acute-lymphoblastic-leukemia
#17
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
https://www.readbyqxmd.com/read/27494089/health-related-quality-of-life-and-patient-reported-outcomes-of-ofatumumab-plus-chlorambucil-versus-chlorambucil-monotherapy-in-the-complement-1-trial-of-patients-with-previously-untreated-cll
#18
Peter Hillmen, Ann Janssens, K Govind Babu, Janusz Kloczko, Sebastian Grosicki, Stephanie Manson, Astrid McKeown, Ira Gupta, Chai-Ni Chang, Fritz Offner
BACKGROUND: Patients diagnosed with chronic lymphocytic leukemia (CLL) are usually elderly and frequently have a number of comorbidities. Health-related quality of life (HRQoL) for these patients is of utmost importance and should be taken into consideration when assessing new treatment options. The combination of ofatumumab with chlorambucil has shown longer progression-free survival compared with chlorambucil alone. In this study, we aim to assess how this treatment combination affects patients' health-related quality of life and patient-reported symptoms...
September 2016: Acta Oncologica
https://www.readbyqxmd.com/read/27493712/ofatumumab-plus-chlorambucil-as-a-first-line-therapy-in-less-fit-patients-with-chronic-lymphocytic-leukemia-analysis-of-complement1-and-other-monoclonal-antibodies-association-data
#19
REVIEW
Anna Maria Frustaci, Alessandra Tedeschi, Paola Picardi, Maddalena Mazzucchelli, Roberto Cairoli, Marco Montillo
The management of patients with chronic lymphocytic leukemia (CLL) has radically improved over the last few years with the addition of anti-CD20 monoclonal antibodies (MoAbs) to chemotherapy. Chlorambucil has been considered for decades as a suitable therapeutic option for frail patients. Taking into account the advantage offered by the addition of MoAbs to chemotherapy, different studies up to now have explored the feasibility of chlorambucil-based chemoimmunotherapies in treatment-naïve CLL. COMPLEMENT1 is a prospective, randomized, open-label trial evaluating the efficacy and safety of ofatumumab added to chlorambucil, compared with chlorambucil in monotherapy, in the setting of untreated patients with CLL considered unsuitable for a fludarabine-based approach...
August 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27485081/perspectives-of-ofatumumab-as-cd20-targeted-therapy-in-rheumatoid-arthritis-and-other-autoimmune-diseases
#20
Yves Marie Pers, Christian Jorgensen
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition viewed as a severe destructive disease. The treatment strategies include anti-CD20 monoclonal antibody (mAb)-targeting B cells. Ofatumumab specifically targets a membrane-proximal epitope on the CD20 molecule distinct from other anti-CD20 antibodies including rituximab and ocrelizumab, and bind the epitope located on the large loop of CD20. This explains a more durable B-cell depletion and a different pharmacodynamic. We review the pharmacodynamic of B-cell depletion and analyze the results in RA and other B-cell-mediated autoimmune diseases...
September 2016: Immunotherapy
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