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Hermann Einsele, Martin Schreder
Elotuzumab is a humanized monoclonal antibody targeting the extracellular domain of signaling lymphocytic activation molecule F7 (SLAMF7) highly expressed in multiple myeloma cells. Upon binding to myeloma cells, elotuzumab exerts its cytotoxic effects through antibody-dependent cellular cytotoxicity, the antibody-induced selective lysis of tumor cells by activated natural killer (NK) cells. Furthermore, elotuzumab has been shown to directly induce NK-cell activation by binding to SLAMF7 expressed on NK cells and to indirectly modulate T-cell function by promoting the secretion of cytokines from NK cells...
October 2016: Therapeutic Advances in Hematology
Lisa A Raedler
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
Laurent Garderet, Gordon Cook, Holger W Auner, Benedetto Bruno, Henk Lokhorst, Jose Antonio Perez-Simon, Firoozeh Sahebi, Christof Scheid, Curly Morris, Anja van Biezen, Mohamad Sobh, Mauricette Michallet, Gösta Gahrton, Stefan Schönland, Nicolaus Kröger
Major improvements have been made in the treatment of myeloma. However, all patients, perhaps with some exceptions, eventually relapse, even after autologous stem cell transplantation (ASCT). In that setting, the combinations of new drugs, namely the IMiDs and the proteasome inhibitors along with steroids, give encouraging results in relapsed patients. The median progression-free survival (PFS) is 20 months with lenalidomide plus dexamethasone plus ixazomib and 26 months with lenalidomide plus dexamethasone plus carfilzomib...
September 21, 2016: Leukemia & Lymphoma
John H Stone
IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that can affect essentially any organ. The disease shows similar histopathology findings across organ systems, consisting of a lymphoplasmacytic infiltrate enriched in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. IgG4 itself appears to be a reactive phenomenon rather than the primary disease driver. Recent investigations have focused on the interactions between cells of the B cell lineage and a novel CD4+ SLAMF7+ cytotoxic T cells capable of promoting fibrosis...
July 2016: Clinical and Experimental Rheumatology
Sagar Lonial, Jonathan Kaufman, Donna Reece, Maria-Victoria Mateos, Jacob Laubach, Paul Richardson
INTRODUCTION: In 2015, 4 new drugs were approved for the treatment of patients with multiple myeloma who experience drug resistance and relapsing disease, offering potential for improved patient outcomes. Given the mortality, morbidity, and projected rise in the incidence of multiple myeloma, more effective, novel therapies and treatment combinations are needed for patients at each stage of the disease. AREAS COVERED: Here, the authors examine published data regarding the development and clinical investigation of elotuzumab, a SLAMF7-targeted monoclonal antibody, for treatment of patients with multiple myeloma...
October 2016: Expert Opinion on Biological Therapy
Hila Magen, Eli Muchtar
Elotuzumab is a monoclonal antibody directed against the SLAMF7 receptor, expressed on normal and malignant plasma cells with a lower expression on other lymphoid cells such as natural killer (NK) cells. Elotuzumab has no significant antimyeloma activity when given as a single agent to patients with relapsed or refractory multiple myeloma (RRMM). However, when combined with other antimyeloma agents, it results in improved response and outcome. Owing to the results from the landmark ELOQUENT-2 phase III clinical trial, which compared lenalidomide and dexamethasone with or without elotuzumab in patients with RRMM, elotuzumab in combination with lenalidomide and dexamethasone was approved by the American Food and Drug Administration (FDA) in November 2015 for multiple myeloma (MM) patients who received one to three prior lines of therapy...
August 2016: Therapeutic Advances in Hematology
Yucai Wang, Larysa Sanchez, David S Siegel, Michael L Wang
Elotuzumab is one of the first two monoclonal antibodies that gained FDA approval for the treatment of multiple myeloma (MM). It targets SLAMF7, which is highly expressed in normal plasma and MM cells as well as natural killer (NK) cells. Elotuzumab demonstrated significant anti-myeloma activity in preclinical studies, and its mechanisms of action include mediating antibody-dependent cell-mediated cytotoxicity, enhancing cytotoxicity of NK cells, and inhibiting MM cell interaction with bone marrow stromal cells...
2016: Journal of Hematology & Oncology
Jean-Samuel Boudreault, Cyrille Touzeau, Philippe Moreau
INTRODUCTION: Multiple myeloma (MM), a mature B-cell neoplasm, is the second most common hematologic malignancy worldwide. Despite significant improvements in outcome with new therapies, the majority of responding patients will eventually develop resistance to treatment. Furthermore, patients swith disease refractory to both proteasome inhibitors and immunomodulatory drugs (IMiDs) have a poor prognosis. AREAS COVERED: Several new therapeutic approaches are emerging and immunotherapeutic strategies present an important advance for the treatment of patients with relapsed or refractory MM...
July 18, 2016: Expert Review of Clinical Immunology
Jennifer Postelnek, Robert J Neely, Michael D Robbins, Carol R Gleason, Jon E Peterson, Steven P Piccoli
Elotuzumab is a first in class humanized IgG1 monoclonal antibody for the treatment of multiple myeloma (MM). Elotuzumab targets the glycoprotein signaling lymphocyte activation molecule family 7 (SLAMF7, also described as CS1 or CRACC) which is expressed on the surface of myeloma cells and a subset of immune cells, including natural killer cells. A soluble version of SLAMF7 (sSLAMF7) has also been reported in MM patients but has not been evaluated as a potential biomarker following therapeutic intervention...
July 2016: AAPS Journal
Katharina Lisenko, Stefan O Schönland, Anna Jauch, Mindaugas Andrulis, Christoph Röcken, Anthony D Ho, Hartmut Goldschmidt, Ute Hegenbart, Michael Hundemer
Systemic amyloid light chain (AL) amyloidosis is a life-threatening protein deposition disorder; however, effective therapy can dramatically improve the prognosis of AL patients. Therefore, accurate diagnosis of the underlying hematologic disease is important. Multi-parameter flow cytometry (MFC) is a reliable method to analyze lymphatic neoplasias and to detect even a small lymphatic clone. We analyzed the presence of clonal plasma cell (PC) and B cells in the bone marrow of 63 patients with newly diagnosed AL amyloidosis by MFC...
July 2016: Cancer Medicine
Salma Afifi, Angela Michael, Alexander Lesokhin
OBJECTIVE: To review the clinical pharmacology, efficacy, and safety of daratumumab and elotuzumab for the treatment of relapsed refractory multiple myeloma (RRMM). DATA SOURCES: A literature search of MEDLINE, PubMed, the US National Institutes of Health, the Food and Drug administration, and relevant meeting abstracts was conducted using the terms daratumumab, elotuzumab, multiple myeloma, anti-CD38, HuMax-CD38, HuLuc63, SLAMF7, and anti-CS1 STUDY SELECTION/DATA EXTRACTION: Human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of daratumumab and elotuzumab for MM were identified...
July 2016: Annals of Pharmacotherapy
Hamid Mattoo, Vinay S Mahajan, Takashi Maehara, Vikram Deshpande, Emanuel Della-Torre, Zachary S Wallace, Maria Kulikova, Jefte M Drijvers, Joe Daccache, Mollie N Carruthers, Flavia V Castelino, James R Stone, John H Stone, Shiv Pillai
BACKGROUND: IgG4-related disease (IgG4-RD) is a systemic condition of unknown cause characterized by highly fibrotic lesions with dense lymphoplasmacytic infiltrates. CD4(+) T cells constitute the major inflammatory cell population in IgG4-RD lesions. OBJECTIVE: We used an unbiased approach to characterize CD4(+) T-cell subsets in patients with IgG4-RD based on their clonal expansion and ability to infiltrate affected tissue sites. METHODS: We used flow cytometry to identify CD4(+) effector/memory T cells in a cohort of 101 patients with IgG4-RD...
September 2016: Journal of Allergy and Clinical Immunology
Sagar Lonial
The recent explosion of immune-based treatments for cancer has significantly impacted remission durations and overall survival for many diseases. Multiple myeloma is no exception to this trend, with several immune-based treatments including checkpoint blockade, cellular therapy, and most advanced now antibody-based treatment coming to fruition. While the use of monoclonal antibodies has been a significant interest in myeloma for some time, identifying the ideal target has been an issue. Given the dependence of plasma cells on interleukin 6 signaling for survival and proliferation, there were several trials testing both single agent and combination therapy effects of anti-interleukin 6 antibodies, which did not demonstrate significant clinical activity; however, more recent antibodies targeting receptors such as CD38 and SLAMF7 (previously known as CS1) are demonstrating significant clinical benefit...
January 2016: Cancer Journal
Anthony Markham
Elotuzumab (Empliciti™) is a humanised IgG1 monoclonal antibody developed by Bristol-Myers Squibb (BMS) and AbbVie that has been approved as combination therapy with lenalidomide and dexamethasone for relapsed/refractory multiple myeloma in the US. Elotuzumab binds to the cell surface receptor signalling lymphocytic activation molecule F7 (SLAMF7), which is selectively expressed on myeloma cells and natural killer cells, leading to antibody-dependent cellular cytotoxicity and direct natural killer cell activation...
March 2016: Drugs
Paul G Richardson, Sundar Jagannath, Philippe Moreau, Andrzej J Jakubowiak, Marc S Raab, Thierry Facon, Ravi Vij, Darrell White, Donna E Reece, Lotfi Benboubker, Jeffrey Zonder, L Claire Tsao, Kenneth C Anderson, Eric Bleickardt, Anil K Singhal, Sagar Lonial
BACKGROUND: Elotuzumab, an immunostimulatory monoclonal antibody targeting signalling lymphocytic activation molecule (SLAM) family member 7 (SLAMF7), selectively kills SLAMF7-expressing myeloma cells through direct activation and engagement of the innate immune system, and thus might have clinical benefit in the treatment of myeloma. In phase 1 of this phase 1b-2 study, 82% of patients with relapsed multiple myeloma who were given elotuzumab plus lenalidomide and dexamethasone achieved an overall response...
December 2015: Lancet Haematology
Alissa Poh
In the last few weeks, the FDA approved three new therapies for multiple myeloma: ixazomib, the first oral proteasome inhibitor; and daratumumab and elotuzumab, two monoclonal antibodies that target CD38 and SLAMF7, respectively.
January 2016: Cancer Discovery
Andrea de Faria F Belone, Patrícia S Rosa, Ana P F Trombone, Luciana R V Fachin, Cássio C Guidella, Somei Ura, Jaison A Barreto, Mabel G Pinilla, Alex F de Carvalho, Dirce M Carraro, Fernando A Soares, Cleverson T Soares
Leprosy, an infectious disease caused by Mycobacterium leprae, affects millions of people worldwide. However, little is known regarding its molecular pathophysiological mechanisms. In this study, a comprehensive assessment of human mRNA was performed on leprosy skin lesions by using DNA chip microarrays, which included the entire spectrum of the disease along with its reactional states. Sixty-six samples from leprotic lesions (10TT, 10BT, 10BB, 10BL, 4LL, 14R1, and 10R2) and nine skin biopsies from healthy individuals were used as controls (CC) (ages ranged from 06 to 83 years, 48 were male and 29 female)...
2015: Frontiers in Genetics
Niels W C J van de Donk, Philippe Moreau, Torben Plesner, Antonio Palumbo, Francesca Gay, Jacob P Laubach, Fabio Malavasi, Hervé Avet-Loiseau, Maria-Victoria Mateos, Pieter Sonneveld, Henk M Lokhorst, Paul G Richardson
Immunotherapeutic strategies are emerging as promising therapeutic approaches in multiple myeloma (MM), with several monoclonal antibodies in advanced stages of clinical development. Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM, and preliminary results from studies with relapsed/refractory patients have shown enhanced therapeutic efficacy when daratumumab and isatuximab are combined with other agents. Furthermore, although elotuzumab (anti-SLAMF7) has no single agent activity in advanced MM, randomized trials in relapsed/refractory MM have demonstrated significantly improved progression-free survival when elotuzumab is added to lenalidomide-dexamethasone or bortezomib-dexamethasone...
February 11, 2016: Blood
Emmanuelle Le Ray, Sundar Jagannath, Antonio Palumbo
The development of proteasome inhibitors (PIs) and immunomodulatory drugs has significantly improved outcomes for patients with relapsed/refractory multiple myeloma (RRMM); however, not all patients benefit from treatment with these agents and some patients can become drug refractory over time. Due to the largely incurable nature of multiple myeloma, the development of newer agents is ongoing and includes new oral PIs (ixazomib), immunotherapies (e.g., CD38- or SLAMF7-targeted antibodies), and small molecules...
January 2016: Expert Review of Hematology
Taimur Sher, Morie A Gertz
Monoclonal antibodies have made an indelible impact on cancer practice. Historically multiple myeloma (MM) has lagged behind in benefitting from this treatment modality. Recent years have seen a tremendous increase in the number of therapeutic antibodies being developed for treatment of MM. Un-conjugated anti-CD 38 antibody Daratumumab and the anti-SLAMF7 antibody elotuzumab are in advanced stages of development and are expected to have a major impact in the management of MM. The immunotoxin Indatuximab Ravtansine is in early stages of development and the results appear encouraging...
September 16, 2015: Leukemia & Lymphoma
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