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Multiple Myeloma, Bortezomib

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https://www.readbyqxmd.com/read/28107546/bone-marrow-stroma-protects-myeloma-cells-from-cytotoxic-damage-via-induction-of-the-oncoprotein-muc1
#1
Michal Bar-Natan, Dina Stroopinsky, Katarina Luptakova, Maxwell D Coll, Arie Apel, Hasan Rajabi, Athalia R Pyzer, Kristen Palmer, Michaela R Reagan, Myrna R Nahas, Rebecca Karp Leaf, Salvia Jain, Jon Arnason, Irene M Ghobrial, Kenneth C Anderson, Donald Kufe, Jacalyn Rosenblatt, David Avigan
Multiple myeloma (MM) is a lethal haematological malignancy that arises in the context of a tumour microenvironment that promotes resistance to apoptosis and immune escape. In the present study, we demonstrate that co-culture of MM cells with stromal cells results in increased resistance to cytotoxic and biological agents as manifested by decreased rates of cell death following exposure to alkylating agents and the proteosome inhibitor, bortezomib. To identify the mechanism of increased resistance, we examined the effect of the co-culture of MM cells with stroma cells, on expression of the MUC1 oncogene, known to confer tumour cells with resistance to apoptosis and necrosis...
January 20, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28105211/diagnostic-and-therapeutic-approaches-to-multiple-myeloma-patients-real-world-data-from-representative-multicentre-treatment-surveys-in-germany-between-2008-and-2011
#2
Thomas M Moehler, Maximilian Merz, Lenka Kellermann, Hartmut Goldschmidt, Wolfgang Knauf
A survey was conducted to investigate the standard of care for multiple myeloma in Germany, in order to clarify the status of implementation of international and national treatment guidelines. In addition, the changes in disease management over time were investigated by comparison with surveys conducted in 2008 and 2009. The survey captured a representative sample of 478 myeloma patients with a mean age of 67.9 years across various stages of the disease. Diagnostic approaches, prognostic aspects and treatment decisions were evaluated based on a survey conducted in 2011 in 58 representative centres in Germany, including university and non-university hospitals and office-based haematologists...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101809/sequential-exposure-of-bortezomib-and-vorinostat-is-synergistic-in-multiple-myeloma-cells
#3
Charvi Nanavati, Donald E Mager
PURPOSE: To examine the combination of bortezomib and vorinostat in multiple myeloma cells (U266) and xenografts, and to assess the nature of their potential interactions with semi-mechanistic pharmacodynamic models and biomarkers. METHODS: U266 proliferation was examined for a range of bortezomib and vorinostat exposure times and concentrations (alone and in combination). A non-competitive interaction model was used with interaction parameters that reflect the nature of drug interactions after simultaneous and sequential exposures...
January 18, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28101022/necrobiotic-xanthogranuloma-in-a-patient-with-multiple-myeloma
#4
Marlies Wruhs, Robert Feldmann, Isabelle Sawetz, Friedrich Breier, Andreas Steiner
An 82-year-old woman presented with a 9-month history of multiple, well-defined skin lesions on her neck and upper chest, progressively increasing in size. Histological examination of a skin biopsy showed a regular epidermis. In the dermis, granulomatous changes with central necrobiosis were found which extended focally into the subcutaneous fat. The necrobiotic areas were surrounded by Touton cells and foreign-body giant cells. Laboratory analysis revealed leucopenia. Serum electrophoresis and immunofixation disclosed the presence of an IgG-λ paraprotein...
September 2016: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28099937/inactivation-of-ck1%C3%AE-in-multiple-myeloma-empowers-drug-cytotoxicity-by-affecting-akt-and-%C3%AE-catenin-survival-signaling-pathways
#5
Sabrina Manni, Marilena Carrino, Martina Manzoni, Ketty Gianesin, Sara Canovas Nunes, Matteo Costacurta, Laura Quotti Tubi, Paolo Macaccaro, Elisa Taiana, Anna Cabrelle, Gregorio Barilà, Annalisa Martines, Renato Zambello, Laura Bonaldi, Livio Trentin, Antonino Neri, Gianpietro Semenzato, Francesco Piazza
Recent evidence indicates that protein kinase CK1α may support the growth of multiple myeloma (MM) plasma cells. Here, by analyzing a large cohort of MM cases, we found that high CK1α mRNA levels are virtually associated with all MM patients. Moreover, we provided functional evidence that CK1α activity is essential for malignant plasma cell survival even in the protective niche generated by co-cultures with bone marrow stromal cells. We demonstrated that CK1α inactivation, while toxic for myeloma cells, is dispensable for the survival of healthy B lymphocytes and stromal cells...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099912/bone-marrow-micro-environment-is-a-crucial-player-for-myelomagenesis-and-disease-progression
#6
Patrizia Mondello, Salvatore Cuzzocrea, Michele Navarra, Michael Mian
Despite the advent of many therapeutic agents, such as bortezomib and lenalidomide that have significantly improved the overall survival, multiple myeloma remains an incurable disease. Failure to cure is multifactorial and can be attributed to the underlying genetic heterogeneity of the cancer and to the surrounding micro-environment. Understanding the mutual interaction between myeloma cells and micro-environment may lead to the development of novel treatment strategies able to eradicate this disease. In this review we discuss the principal molecules involved in the micro-environment network in multiple myeloma and the currently available therapies targeting them...
January 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28092421/carfilzomib-lenalidomide-and-dexamethasone-in-patients-with-heavily-pretreated-multiple-myeloma-a-phase-1-study-in-japan
#7
Kenshi Suzuki, Masaki Ri, Takaaki Chou, Isamu Sugiura, Naoki Takezako, Kazutaka Sunami, Tadao Ishida, Tohru Izumi, Shuji Ozaki, Yoshihisa Shumiya, Kenji Ota, Shinsuke Iida
This is the first study in which the carfilzomib, lenalidomide, and dexamethasone (KRd) regimen was evaluated in heavily pretreated multiple myeloma. This study is a multicenter, open-label phase 1 study of KRd in Japanese patients with relapsed or refractory multiple myeloma (RRMM). The objectives were to evaluate the safety, tolerability, efficacy and pharmacokinetics. Carfilzomib was administrated intravenously over 10 min on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. In cycle 1, the dosage for days 1 and 2 was 20 mg/m(2) , followed by 27 mg/m(2) ...
January 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28091419/two-secondary-primary-malignancies-after-bortezomib-therapy-for-multiple-myeloma-a-single-center-experience
#8
Tian-Jiao Guo, Xiao-Jun Huang, Lei Wen, Jin Lu
No abstract text is available yet for this article.
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28088784/a-phase-i-clinical-study-of-autologous-dendritic-cell-therapy-in-patients-with-relapsed-or-refractory-multiple-myeloma
#9
Sung-Hoon Jung, Hyun-Ju Lee, Youn-Kyung Lee, Deok-Hwan Yang, Hyeoung-Joon Kim, Joon Haeng Rhee, Frank Emmrich, Je-Jung Lee
Cellular immunotherapy is emerging as a potential immunotherapeutic modality in multiple myeloma (MM). We have developed potent immunotherapeutic agent (VAX-DC/MM) generated by dendritic cells (DCs) loaded with autologous myeloma cells irradiated with ultraviolet B. In this study, we evaluated the safety and efficacy of VAX-DC/MM in patients with relapsed or refractory MM. This trial enrolled relapsed or refractory MM patients who had received both thalidomide- and bortezomib-based therapies. Patients received the intradermal VAX-DC/MM injection every week for 4 weeks...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28079515/efficacy-and-safety-of-subcutaneous-versus-intravenous-bortezomib-in-multiple-myeloma-a%C3%A2-meta-analysis%C3%A2
#10
Bin Hu, Quan Zhou, Tao Wu, Lan Zhuang, Liping Yi, Jinxia Cao, Xin Yang, Jun Wang
PURPOSE: We performed this meta-analysis to compare the efficacy and safety between two different administration routes of bortezomib, subcutaneous and intravenous. METHODS: Six retrospective studies and three randomized controlled trials (RCTs) were included in our study. Data from retrospective studies or RCTs were pooled and displayed in their corresponding subgroup, retrospective studies subgroup or RCTs subgroup. We comprehensively compared the overall response rate (ORR) and the incidence of adverse events between subcutaneous and intravenous bortezomib...
January 12, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28079010/discovery-of-natural-product-proteasome-inhibitors-as-novel-anticancer-therapeutics-current-status-and-perspectives
#11
Hui Wang, Qingzhu Yang, Ping Dou, Huanjie Yang
Natural products serve as a main resource for drug discovery. The ubiquitin-proteasome system (UPS) is one of the primary intracellular protein degradation systems, which is responsible for the degradation of most short-lived, mis-folded and aged proteins. The proteasome is a validated target for cancer treatment, since cancer cells are more reliant on high levels of proteasome activity to maintain the dynamic protein homeostasis required for enhanced metabolism and unrestricted proliferation inherent in cancer cells...
January 11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28076695/deacetylase-inhibitors-an-advance-in-myeloma-therapy
#12
Jacob P Laubach, Jesus F San-Miguel, Vania Hungria, Jian Hou, Philippe Moreau, Sagar Lonial, Jae Hoon Lee, Hermann Einsele, Melissa Alsina, Paul G Richardson
A significant unmet need exists in patients with relapsed or refractory multiple myeloma (MM), which remains an incurable disease despite recent advances in the field. One such development was the use of deacetylase inhibitors (DACi), which exert unique antimyeloma effects through targeting of epigenetic and protein metabolism pathways. The pan-DACi panobinostat was recently approved in combination with bortezomib and dexamethasone for use in patients with relapsed or relapsed and refractory MM. Results of a phase 3 trial showed that the panobinostat-containing regimen improved the overall response rate and progression-free survival...
January 11, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28074255/bortezomib-containing-regimens-bcr-for-the-treatment-of-non-transplant-eligible-multiple-myeloma
#13
Victor H Jimenez-Zepeda, Peter Duggan, Paola Neri, Jason Tay, Nizar J Bahlis
In multiple myeloma (MM) patients ineligible for transplant, the selection of up-front therapy needs to balance efficacy and toxicity. Recently, regimens with bortezomib, a proteasome inhibitor with anti-myeloma effects, have been reported. We aimed to evaluate the impact of different bortezomib-containing regimens (BCR) for the treatment of transplant-ineligible MM. All- consecutive patients treated with BCR at our institution from 01/05 to 02/16 were evaluated. With a median of 6 cycles, an overall response rate of 95...
January 10, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28074071/olaptesed-pegol-an-anti-cxcl12-sdf-1-spiegelmer-%C3%A2-alone-and-with-bortezomib-dexamethasone-in-relapsed-refractory-multiple-myeloma-a-phase-iia-study
#14
H Ludwig, K Weisel, M T Petrucci, X Leleu, A M Cafro, L Garderet, C Leitgeb, R Foa, R Greil, I Yakoub-Agha, D Zboralski, S Vauléon, T Dümmler, D Beyer, Ana Kruschinski, K Riecke, M Baumann, M Engelhardt
Leukemia accepted article preview online, 11 January 2017. doi:10.1038/leu.2017.5.
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28072730/bortezomib-combined-with-lenalidomide-as-the-first-line-treatment-for-the-rare-synchronous-occurrence-of-multiple-myeloma-and-pulmonary-adenocarcinoma-a-case-report
#15
Wenli Zuo, Xinghu Zhu, Jingke Yang, Zhenyang Mei, Mei Deng, Quande Lin, Yongping Song, Qingsong Yin
BACKGROUND: Simultaneous multiple myeloma (MM) and pulmonary adenocarcinoma is a rare occurrence, and thus, treatment is a challenge. This study reports on 1 such case of MM with concurrent lung cancer, where an accurate diagnosis was made and the patient underwent treatment for both cancers. CASE SUMMARY: A 68-year-old man presented with 2 months of progressive lower back pain. Visualization with magnetic resonance imaging (MRI) revealed multiple collapsed vertebrae from T12 to S3, as well as an altered signal intensity at the T3 vertebra...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28070715/an-integrated-assessment-of-the-effects-of-immunogenicity-on-the-pharmacokinetics-safety-and-efficacy-of-elotuzumab
#16
Chaitali Passey, Johanna Mora, Robert Dodge, Leonid Gibiansky, Jennifer Sheng, Amit Roy, Akintunde Bello, Manish Gupta
Elotuzumab is a humanized, immunostimulatory anti-signaling lymphocytic activation molecule F7 (SLAMF7) IgG1 monoclonal antibody indicated in combination with lenalidomide and dexamethasone for patients with multiple myeloma (MM) who have received 1-3 prior therapies. We assessed the immunogenicity of elotuzumab as a monotherapy and in combination with bortezomib/dexamethasone and lenalidomide/dexamethasone in patients with MM in five clinical studies, including the pivotal ELOQUENT-2 trial (NCT01239797). Anti-drug antibody (ADA) prevalence was determined using a validated bridging assay...
January 9, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28069603/treatment-of-b-cell-disorder-improves-renal-outcome-of-patients-with-monoclonal-gammopathy-associated-c3-glomerulopathy
#17
Sophie Chauvet, Véronique Frémeaux-Bacchi, Florent Petitprez, Alexandre Karras, Laurent Daniel, Stéphane Burtey, Gabriel Choukroun, Yahsou Delmas, Dominique Guerrot, Arnaud François, Moglie Le Quintrec, Vincent Javaugue, David Ribes, Laurence Vrigneaud, Bertrand Arnulf, Jean Michel Goujon, Pierre Ronco, Guy Touchard, Frank Bridoux
The high frequency of monoclonal gammopathy in adult patients with C3 glomerulopathy (C3G) emphasizes the role of the monoclonal immunoglobulin (MIg) in the occurrence of renal disease and raises the issue of the therapeutic management. The aim of the study was to evaluate the effect of chemotherapy in a large cohort of patients with MIg-associated C3G. Fifty adult patients with MIg and biopsy-proven C3G were extracted from the French national database of C3G. We retrospectively compared renal outcomes in patients who received or not chemotherapy targeting the underlying B-cell clone...
January 9, 2017: Blood
https://www.readbyqxmd.com/read/28061991/combination-therapy-for-fit-younger-and-older-newly-diagnosed-multiple-myeloma-patients-data-support-carfilzomib-lenalidomide-and-dexamethasone-independent-of-cytogenetic-risk-status
#18
REVIEW
Ola Landgren
In this invited paper, I was asked to critically review available literature and seek scientific and clinical evidence to argue in support of carfilzomib, lenalidomide, and dexamethasone (KRd) as the new default therapy for fit patients with a new diagnosis of multiple myeloma (MM). When performing the review of existing data and when writing this paper it became clear to me that both KRd and bortezomib, lenalidomide, and dexamethasone (RVd) are both recommended by established, well-respected expert guidelines...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28060563/efficacy-and-safety-of-elotuzumab-for-the-treatment-of-multiple-myeloma
#19
Maria Gavriatopoulou, Evangelos Terpos, Efstathios Kastritis, Meletios A Dimopoulos
Multiple myeloma (MM) is the second most common hematologic malignancy and despite significant outcome improvements with novel agents, the majority of patients will eventually relapse and develop treatment resistance. Immunotherapy is emerging as a promising therapeutic approach in MM. Areas covered: Elotuzumab is a monoclonal antibody directly targeting the SLAMF7 receptor, expressed on normal and malignant plasma cells. Elotuzumab has no meaningful antimyeloma activity when given as monotherapy to patients with relapsed or refractory MM (RRMM)...
January 6, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28053546/comparing-efficacy-and-survivals-of-initial-treatments-for-elderly-patients-with-newly-diagnosed-multiple-myeloma-a-network-meta-analysis-of-randomized-controlled-trials
#20
Xiaoping Liu, Jiarui Chen, Yuncen A He, Xiangyu Meng, Kaili Li, Colin K He, Shangqin Liu
OBJECTIVE: The aim of this study was to evaluate the efficacy and clinical outcome of initial therapies for elderly patients with multiple myeloma (MM). METHODS: Randomized controlled trials (RCTs) were obtained through a comprehensive search. Response rate, progression-free survival (PFS) and overall survival (OS) were the interested outcome measures. Network meta-analysis (NMA) using graph theory methodology to construct an NMA model, and sensitivity analysis were performed...
2017: OncoTargets and Therapy
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