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Michele Moschetta, Yawara Kawano, Klaus Podar
Unprecedented advances in multiple myeloma (MM) therapy during the last 15 years are predominantly based on our increasing understanding of the pathophysiologic role of the bone marrow (BM) microenvironment. Indeed, new treatment paradigms, which incorporate thalidomide, immunomodulatory drugs (IMiDs), and proteasome inhibitors, target the tumor cell as well as its BM microenvironment. Ongoing translational research aims to understand in more detail how disordered BM-niche functions contribute to MM pathogenesis and to identify additional derived targeting agents...
2016: Cancer Treatment and Research
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
Peter M Voorhees, Saad Z Usmani
The advent of the immunomodulatory drugs thalido-mide, lenalidomide, and pomalidomide; the proteasome inhib-itors bortezomib, carfilzomib, and ixazomib; the histone deacet-ylase inhibitor panobinostat; and the monoclonal antibodies elotuzumab and daratumumab has led to dramatic improvements in outcomes for patients with multiple myeloma. Along with progress in nontransplant therapy have come questions regarding the continued role of high-dose melphalan (HDM) supported by autologous stem cell transplant (ASCT) in the treatment of multiple myeloma...
September 2016: Clinical Advances in Hematology & Oncology: H&O
Lisa A Raedler
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
Kazunori Murata, Samuel I McCash, Brittany Carroll, Alexander M Lesokhin, Hani Hassoun, Nikoletta Lendvai, Neha S Korde, Sham Mailankody, Heather J Landau, Guenther Koehne, David J Chung, Sergio A Giralt, Lakshmi V Ramanathan, Ola Landgren
OBJECTIVES: To characterize the effect of three humanized IgG κ monoclonal antibodies (daratumumab, isatuximab, and elotuzumab) on the interpretation of results generated by protein electrophoresis, immunofixation, free light chain, and heavy/light chain assays performed on human serum. METHODS: Healthy volunteer serum and serum from multiple myeloma patients were supplemented with clinically relevant concentrations of each of the three monoclonal antibodies. These specimens then underwent analysis via serum protein electrophoresis, immunofixation, serum free light chain quantification, heavy/light chain quantification, total IgG, and total protein...
September 21, 2016: Clinical Biochemistry
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
Binod Dhakal, Saulius Girnius, Parameswaran Hari
There have been major recent advancements in the understanding and management of multiple myeloma. Diagnostic criteria have been revised and former ultra-high-risk smoldering multiple myeloma is now considered multiple myeloma in need of treatment. Understanding clonal progression, evolution, and tides not only has helped elucidate the disease behavior but might help expand therapeutic choices in order to select appropriate treatment for patients. Unprecedented response rates with modern triplet induction therapies containing proteasome inhibitor and immunomodulators have made this approach standard for initial treatment...
2016: F1000Research
Junshik Hong, Jae Hoon Lee
Epidemiologically, multiple myeloma (MM) is a malignant disorder of plasma cells with a higher incidence among Western populations than among Asians. However, there is growing evidence of a recent increase in the age-standardized incidence rate (ASR) of MM in Asian countries, particularly Korea. Application of novel agents has resulted in significant improvement of treatment outcomes, and the advances are ongoing with the recent introduction and U.S. Food and Drug Administration's approval of newer agents, including carfilzomib, ixazomib, elotuzumab, and daratumumab...
September 2016: Korean Journal of Internal Medicine
J Aubrey Waddell, Dominic A Solimando
The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast...
July 2016: Hospital Pharmacy
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
A M Rajan, S Kumar
The treatment of multiple myeloma (MM) is rapidly evolving. In the United States, four drugs (panobinostat, ixazomib, daratumumab and elotuzumab) were approved for the treatment of MM in 2015. As a result of improved diagnosis and therapy, there has been a dramatic improvement in the outcome of MM in the last decade, probably more than any other malignancy. Numerous agents continue to be studied in preclinical models and in clinical trials, with many demonstrating clinical efficacy that appears promising enough to have a trajectory for regulatory approval...
2016: Blood Cancer Journal
María-Victoria Mateos, Miguel Granell, Albert Oriol, Joaquin Martinez-Lopez, Joan Blade, Miguel T Hernandez, Jesus Martín, Mercedes Gironella, Mark Lynch, Eric Bleickardt, Prashni Paliwal, Anil Singhal, Jesus San-Miguel
Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-200 mg and dexamethasone 40 mg (with/without cyclophosphamide 50 mg) in patients with relapsed/refractory multiple myeloma (RRMM). The primary endpoint was the proportion of grade ≥3 non-haematological adverse events (AEs); other endpoints included the number of dose reductions/discontinuations and efficacy...
July 19, 2016: British Journal of Haematology
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
Leonard Naymagon, Maher Abdul-Hay
Multiple myeloma (MM) is a disease that affects plasma cells and can lead to devastating clinical features such as anemia, lytic bone lesions, hypercalcemia, and renal disease. An enhanced understanding of MM disease mechanisms has led to new more targeted treatments. There is now a plethora of treatments available for MM. In this review article, our aim is to discuss many of the novel agents that are being studied or have recently been approved for the treatment of MM. These agents include the following: immunomodulators (pomalidomide), proteasome inhibitors (carfilzomib, marizomib, ixazomib, oprozomib), alkylating agents (bendamustine), AKT inhibitors (afuresertib), BTK inhibitors (ibrutinib), CDK inhibitors (dinaciclib), histone deacetylase inhibitors (panobinostat, rocilinostat, vorinostat), IL-6 inhibitors (siltuximab), kinesin spindle protein inhibitors (filanesib), monoclonal antibodies (daratumumab, elotuzumab, indatuximab, SAR650984), and phosphoinositide 3-kinase (PI3K) inhibitors...
2016: Journal of Hematology & Oncology
Sebastian Grosicki, Agnieszka Barchnicka
INTRODUCTION: Multiple myeloma (MM), constantly remains debilitating disease, consequently leading to death. Clinical trials involving drugs with different mechanisms of action, carry the expectancy for improvement of treatment outcomes. The results of the currently published studies on the monoclonal antibodies, in particular elotuzumab confirm previous expectations of improving treatment outcomes of such therapy in MM patients. AREAS COVERED: This humanized monoclonal antibody targeting surface glycoprotein CS1, expressed commonly on plasma cells and certain cells of the immune system, stimulates the immune system to fight against MM cells...
July 2016: Expert Review of Hematology
Dennis J Cada, Jessica Dang, Danial E Baker
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line...
April 2016: Hospital Pharmacy
Nagaraju Anreddy, Lori A Hazlehurst
Multiple myeloma (MM) is a malignant plasma cell disorder, clinically characterized by osteolytic lesions, immunodeficiency, and renal disease. Over the past decade, MM therapy is significantly improved by the introduction of novel therapeutics such as immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), monoclonal antibodies (daratumumab and elotuzumab), histone deacetylase (HDAC) inhibitors (Panobinostat). The clinical success of these agents has clearly identified vulnerabilities intrinsic to the MM cell- as well as targets that emanate from the tumor microenvironment...
June 4, 2016: Journal of Cellular Biochemistry
Flora Zagouri, Evangelos Terpos, Efstathios Kastritis, Meletios A Dimopoulos
INTRODUCTION: Monoclonal antibodies mark the beginning of a new era in the context of multiple myeloma (MM) treatment. Numerous antibodies have been tested or are currently in development for patients with MM, in order to improve tolerability and quality of life. AREAS COVERED: This manuscript reviews emerging antibodies for the treatment of MM i.e. elotuzumab, daratumumab, MOR03087, isatuximab, bevacizumab, cetuximab, siltuximab, tocilizumab, elsilimomab, azintrel, rituximab, tositumomab, milatuzumab, lucatumumab, dacetuzumab, figitumumab, dalotuzumab, AVE1642, tabalumab, pembrolizumab, pidilizumab, nivolumab...
June 2016: Expert Opinion on Emerging Drugs
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