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Multiple Myeloma, Bortezomib

Ying Yu Liang, Ilse Schwarzinger, Ingrid Simonitsch-Klupp, Hermine Agis, Rudolf Oehler
Efficient clearance of apoptotic cells by efferocytosis is important for tissue homeostasis. Impaired efferocytosis leads to the accumulation of cell debris, which is regarded as a trigger in chronic inflammation and autoimmune diseases. Patients with hematological neoplastic disorders such as multiple myeloma (MM) exhibit high blood levels of apoptotic microparticles. The present study investigated whether these high levels of apoptotic microparticles are associated with insufficient dead cell clearance. Blood samples were collected from patients with MM immediately prior to and 3, 7 and 10 days after the initial cycle of bortezomib-based therapy...
July 2018: Oncology Letters
Chuan Wu, Ting Yang, Yingmin Liu, Yicheng Lu, Yanping Yang, Xiaobo Liu, Xuelian Liu, Long Ye, Yue Sun, Xue Wang, Qingchao Li, Peiyu Yang, Xiaoyuan Yu, Sujun Gao, Shaji Kumar, Fengyan Jin, Yun Dai, Wei Li
1q21 gain is a common cytogenetic abnormality featuring high-risk multiple myeloma (HRMM). However, the molecular mechanism underlying the adverse prognostic effect of 1q21 gain remains largely unclear. Here, we report that ARNT/HIF-1β, a 1q21 gene, is highly expressed in HRMM and induced by microenvironmental hypoxia, which confers drug resistance and correlates with inferior outcome. Analysis of the gene expression profile database revealed that ARNT expression was upregulated in MM and increased with disease progression or in HRMM subtypes (particularly 1q21 gain), while correlated to shorter overall survival...
June 21, 2018: Cancer Medicine
Matevz Skerget, Barbara Skopec, Vesna Zadnik, Darja Zontar, Helena Podgornik, Katarina Rebersek, Tadej Furlan, Peter Cernelc
OBJECTIVES: In this retrospective study, we evaluated the impact of CD56, CD117, and CD28 expression on clinical characteristics and survival in newly diagnosed myeloma patients treated with bortezomib-based induction therapy. METHODS: We analyzed 110 myeloma patients. Immunophenotype was determined using panels consisting of CD19/CD38/CD45/CD56/CD138 and CD20, CD28, and CD117 were used additionally. All samples were tested for recurrent chromosomal aberrations...
June 19, 2018: Acta Haematologica
K Luczkowska, Z Litwinska, E Paczkowska, B Machalinski
Multiple myeloma (MM) is a disease of unknown, complex etiology that affects primarily older adults. The course of the disease and the patients' survival time are very heterogeneous, but over the last decade, clear progress in the treatment of this incurable disease has been observed. Therapeutics that have proven to be highly effective include the immunomodulatory drug thalidomide and its newer analogs, lenalidomide and pomalidomide, as well as the proteasome inhibitors bortezomib and carfilzomib. However, the administration of some of the treatments, e...
April 2018: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Yung-Hsing Huang, Ommoleila Molavi, Abdulraheem Alshareef, Moinul Haque, Qian Wang, Michael P Chu, Christopher P Venner, Irwindeep Sandhu, Anthea C Peters, Afsaneh Lavasanifar, Raymond Lai
Malignant cells cultured in three-dimensional (3D) models have been found to be phenotypically and biochemically different from their counterparts cultured conventionally. Since most of these studies employed solid tumor types, how 3D culture affects multiple myeloma (MM) cells is not well understood. Here, we compared MM cells (U266 and RPMI8226) in a 3D culture model with those in conventional culture. While the conventionally cultured cells were present in single cells or small clusters, MM-3D cells grew in large spheroids...
June 16, 2018: Cancers
Young Yun Jung, Jong Hyun Lee, Dongwoo Nam, Acharan S Narula, Ojas A Namjoshi, Bruce E Blough, Jae-Young Um, Gautam Sethi, Kwang Seok Ahn
Because of the essential role of signal transducer and activator of transcription 3 (STAT3) in proliferation, anti-apoptosis, and chemoresistance of multiple myeloma (MM), we investigated whether icariin, a prenylated flavonol glycoside, inhibits both constitutive and inducible STAT3 activation in human myeloma cell lines. We noted that icariin could block constitutive STAT3 phosphorylation as well as its nuclear translocation and DNA binding ability in U266 cells. Icariin also suppressed IL-6-induced STAT3 activation through the inhibition of upstream kinases (Janus activated kinase-1 and -2, and c-Src)...
2018: Frontiers in Pharmacology
Rebecca Epperly, John Ozolek, Kyle Soltys, Debra Cohen, Rakesh Goyal, Erika Friehling
Post-transplant lymphoproliferative disorder (PTLD) related plasma cell neoplasms are rare in pediatric patients. We report a pediatric liver transplant recipient with plasma cell myeloma type PTLD. Cytogenetics included 1q duplication, associated with poor prognosis in adult multiple myeloma, and t(8;14). High-risk cytogenetics has not been reported in pediatric plasma cell myeloma type PTLD. The patient was treated with bortezomib, dexamethasone, and lenalidomide with subsequent autologous stem cell transplant...
June 12, 2018: Pediatric Blood & Cancer
Braden J Lawrence, Emily L Petersen, Wayne G Riches, David C Pfeiffer
Plasmacytomas are rare immunoproliferative monoclonal plasma cell diseases of lymphoid lineage that may present in an isolated or systemic manner. Systemic involvement is much more common than occurrences isolated to a particular organ, and for this reason, it is imperative to rule out systemic involvement for osseous and nonosseous isolated neoplasms. These neoplasms present unique challenges due to their location, extent of involvement, vague presentation, and dearth of treatment protocol. We report the case of a 69-year-old man who developed chronic kidney disease stage 4 between 2009 and 2012...
June 6, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Grzegorz Charlinski, Norbert Grzasko, Artur Jurczyszyn, Mariusz Janczarski, Agnieszka Szeremet, Anna Waszczuk-Gajda, Paweł Bernatowicz, Alina Swiderska, Renata Guzicka-Kazimierczak, Ewa Lech-Maranda, Andrzej Szczepaniak, Ryszard Wichary, Anna Dmoszynska
BACKGROUND: Patients with relapsed/refractory multiple myeloma (RRMM) have poor prognosis. Pomalidomide is an immunomodulatory compound that has demonstrated activity in MM patients with disease refractory to lanlidomide and bortezomib. OBJECTIVES: Participants of clinical trials are highly selected populations; therefore, the aim of this study was to present observations from real practice that might provide important information for practitioners. PATIENTS AND METHODS: We analyzed retrospectively 50 patients treated with pomalidomide in 12 Polish sites between 2014 and 2017...
June 8, 2018: European Journal of Haematology
Mohammad Mahmoudian, Hadi Valizadeh, Parvin Zakeri-Milani
Bortezomib (BTZ), a proteasome inhibitor, is clinically used for the treatment of multiple myeloma and mantle cell lymphoma via intravenous or subcutaneous administration. Since BTZ has limited intestinal permeability, in this study, solid lipid nanoparticles (SLNs) were selected as lipid carrier to improve the intestinal permeability of BTZ. The nanoparticles were prepared by hot oil-in-water emulsification method and characterized for physicochemical properties. Moreover, in situ single-pass intestinal perfusion technique was used for intestinal permeability studies...
June 7, 2018: Drug Development and Industrial Pharmacy
Philippe Moreau, Maria-Victoria Mateos, James R Berenson, Katja Weisel, Antonio Lazzaro, Kevin Song, Meletios A Dimopoulos, Mei Huang, Anita Zahlten-Kumeli, A Keith Stewart
BACKGROUND: Twice a week carfilzomib at 27 mg/m2 is approved for treatment of relapsed or refractory multiple myeloma. Phase 1/2 CHAMPION-1, the first study exploring once-weekly carfilzomib dosing, established the maximum tolerated dose at 70 mg/m2 in combination with dexamethasone. We aimed to compare progression-free survival in patients with relapsed and refractory multiple myeloma given once weekly carfilzomib or twice weekly carfilzomib. METHODS: In this prespecified interim analysis of the randomised, open-label, phase 3 A...
May 31, 2018: Lancet Oncology
Joan Bladé, Laura Rosiñol, María Teresa Cibeira, Carlos Fernández de Larrea
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice...
May 31, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Ajai Chari, Menaka Bhor, Lamis Eldjerou, Adrienne M Gilligan, Alyson Urniasz, Denise Globe, Diana Stetsovsky, Helen Varker, Brian Davis, Machaon Bonafede, James Talcott
AIM: To examine real-world treatment patterns in multiple myeloma (MM) patients treated with panobinostat. MATERIALS & METHODS: Using a US claims database, MM patients treated with panobinostat during 02/01/2015-01/31/2017 were evaluated. Lines of therapy, combination regimens, dosing and duration were measured. RESULTS: Ninety-five patients were included (mean age: 61.4 years). Patients were heavily pretreated, with 88.4% exposed to both a proteasome inhibitor and an immunomodulatory agent...
May 30, 2018: Future Oncology
Sundar Jagannath, Rafat Abonour, Brian G M Durie, Cristina Gasparetto, James W Hardin, Mohit Narang, Howard R Terebelo, Kathleen Toomey, Lynne Wagner, Shankar Srinivasan, Amani Kitali, Lihua Yue, E Dawn Flick, Amit Agarwal, Robert M Rifkin
BACKGROUND: The treatment landscape for multiple myeloma (MM) has undergone recent changes with the regulatory approval of several new therapies indicated for second- and later-line disease. Using data from Connect MM, the largest multisite, primarily community-based, prospective, observational registry of MM patients in the United States, selection of second-line treatments was evaluated during a 5-year period from 2010 to 2016. PATIENTS AND METHODS: Eligible patients were aged ≥ 18 years, had newly diagnosed MM ≤ 2 months before study entry, and were followed for up to 8 years...
May 4, 2018: Clinical Lymphoma, Myeloma & Leukemia
Jamie D Cavenagh, Rakesh Popat
Recent advances in treatment have extended the survival of patients with multiple myeloma. This improvement in itself poses challenges because of the length of time that patients live with myeloma, its physical complications, and toxicities of treatment. Thus, improvements in maintaining quality of life are essential, and part of this challenge involves learning how to optimally use new therapeutic agents. Panobinostat is the first histone deacetylase inhibitor approved for the treatment of multiple myeloma...
May 24, 2018: Clinical Lymphoma, Myeloma & Leukemia
Carlyn Rose C Tan, Saif Abdul-Majeed, Brittany Cael, Stefan K Barta
Proteasome inhibitors disrupt multiple pathways in cells and the bone marrow microenvironment, resulting in apoptosis and inhibition of cell-cycle progression, angiogenesis, and proliferation. Bortezomib is a first-in-class proteasome inhibitor approved for the treatment of multiple myeloma and mantle cell lymphoma after one prior therapy. It is also effective in other plasma cell disorders and non-Hodgkin lymphomas. The main mechanism of action of bortezomib is to inhibit the chymotrypsin-like site of the 20S proteolytic core within the 26S proteasome, thereby inducing cell-cycle arrest and apoptosis...
May 26, 2018: Clinical Pharmacokinetics
Andrew J Cowan, Christine Allen, Aleksandra Barac, Huda Basaleem, Isabela Bensenor, Maria Paula Curado, Kyle Foreman, Rahul Gupta, James Harvey, H Dean Hosgood, Mihajlo Jakovljevic, Yousef Khader, Shai Linn, Deepesh Lad, Lorenzo Mantovani, Vuong Minh Nong, Ali Mokdad, Mohsen Naghavi, Maarten Postma, Gholamreza Roshandel, Katya Shackelford, Mekonnen Sisay, Cuong Tat Nguyen, Tung Thanh Tran, Bach Tran Xuan, Kingsley Nnanna Ukwaja, Stein Emil Vollset, Elisabete Weiderpass, Edward N Libby, Christina Fitzmaurice
Introduction: Multiple myeloma (MM) is a plasma cell neoplasm with substantial morbidity and mortality. A comprehensive description of the global burden of MM is needed to help direct health policy, resource allocation, research, and patient care. Objective: To describe the burden of MM and the availability of effective therapies for 21 world regions and 195 countries and territories from 1990 to 2016. Design and Setting: We report incidence, mortality, and disability-adjusted life-year (DALY) estimates from the Global Burden of Disease 2016 study...
May 16, 2018: JAMA Oncology
Roman Hájek, Jiri Jarkovsky, Vladimír Maisnar, Ludek Pour, Ivan Špička, Jiri Minařík, Evžen Gregora, Petr Kessler, Michal Sýkora, Hana Fraňková, Marco Campioni, Lucy DeCosta, Maarten Treur, Sebastian Gonzalez-McQuire, Walter Bouwmeester
INTRODUCTION: Real-world data on patient outcomes and treatment patterns in multiple myeloma (MM) are limited. MATERIALS AND METHODS: The present noninterventional, observational, retrospective analysis of prospectively collected Czech patient medical record data from the Registry of Monoclonal Gammopathies estimated real-world outcomes in adults with a diagnosis of symptomatic MM made between May 2007 and June 2014. RESULTS: In total, 2446 patients had initiated first-line treatment...
June 2018: Clinical Lymphoma, Myeloma & Leukemia
Magdalini Migkou, Maria Gavriatopoulou, Evangelos Terpos, Meletios Athanasios Dimopoulos
Multiple myeloma prognosis has improved significantly during the past decade, with survival prolongation mainly due to the incorporation of novel agents. Bortezomib represents one of the main backbone agents of antimyeloma treatment. Areas covered: This review aims to identify possible and available therapeutic options for patients who experience disease refractoriness following bortezomib exposure. Expert commentary: For patients who finally relapse after bortezomib exposure treatment strategy should be individualized...
May 28, 2018: Expert Review of Hematology
Shaji K Kumar
The most recent NCCN Guidelines for Multiple Myeloma include a ranking of the many treatment options for various settings as "preferred," "other," and "useful in certain circumstances." For patients eligible for autologous stem cell transplant (ASCT), the preferred regimen remains bortezomib/lenalidomide/dexamethasone (category 1) or bortezomib/cyclophosphamide/dexamethasone. Upfront ASCT also remains a preferred strategy for patients who are transplant-eligible, despite highly effective newer agents such as induction therapy...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
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