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Multiple Myeloma, Bortezomib

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https://www.readbyqxmd.com/read/28734795/monoclonal-antibodies-in-multiple-myeloma-a-new-wave-of-the-future
#1
REVIEW
Daniel W Sherbenou, Tomer M Mark, Peter Forsberg
In 2015, 2 monoclonal antibodies were approved for the treatment of relapsed or refractory multiple myeloma (RRMM), elotuzumab and daratumumab. Elotuzumab is a monoclonal IgG-κ antibody directed against SLAMF7 (signaling lymphocytic activation molecule F7), a cell surface receptor involved in natural killer cell activation. Daratumumab is a monoclonal IgG-κ antibody that binds to CD38, a transmembrane protein found on the surface of myeloma cells and responsible for cellular adhesion and ectoenzymatic activity...
June 27, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28733196/proteasome-subunit-beta-type-1-p11a-polymorphism-is-a-new-prognostic-marker-in-multiple-myeloma
#2
Gergely Varga, Gábor Mikala, Katalin Piroska Kiss, Éva Kosóczki, Edit Szabó, Nóra Meggyesi, Katalin Balassa, Petra Kövy, Bálint Tegze, Gergely Szombath, Attila Tordai, Hajnalka Andrikovics, László Homolya, Tamás Masszi
BACKGROUND: Proteasome subunit beta type 1 (PSMB1) rs12717 polymorphism, a single nucleotide polymorphism with unknown functional effect, was recently reported to influence response to bortezomib-based therapy in follicular lymphoma. PATIENTS AND METHODS: We retrospectively analyzed the prognostic impact of this polymorphism in 211 consecutively diagnosed multiple myeloma cases, and performed in vitro experiments to look into its functional consequences. RESULTS: On univariate analysis, patients carrying the variant G allele showed significantly shorter progression-free survival (PFS) with a pattern suggestive of a gene-dose effect (PFS 26...
June 30, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28729113/activation-of-rage-stat3-pathway-by-methylglyoxal-contributes-to-spinal-central-sensitization-and-persistent-pain-induced-by-bortezomib
#3
Jia-You Wei, Cui-Cui Liu, Han-Dong Ouyang, Chao Ma, Man-Xiu Xie, Meng Liu, Wan-Long Lei, Huan-Huan Ding, Shao-Ling Wu, Wen-Jun Xin
Bortezomib is a first-line chemotherapeutic drug widely used for multiple myeloma and other nonsolid malignancies. Although bortezomib-induced persistent pain is easily diagnosed in clinic, the pathogenic mechanism remains unclear. Here, we studied this issue with use of a rat model of systemic intraperitoneal administration of bortezomib for consecutive 5days. Consisted with our previous study, we found that bortezomib treatment markedly induced mechanical allodynia in rats. Furthermore, we first found that bortezomib treatment significantly induced the upregulation of methylglyoxal in spinal dorsal horn of rats...
July 18, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28725572/novel-panel-of-protein-biomarkers-to-predict-response-to-bortezomib-containing-induction-regimens-in-multiple-myeloma-patients
#4
Kay Reen Ting, Michael Henry, Justine Meiller, Annemarie Larkin, Martin Clynes, Paula Meleady, Despina Bazou, Paul Dowling, Peter O'Gorman
BACKGROUND: Multiple myeloma (MM) is a complex heterogeneous disease. Various risk stratification models have been recommended including cytogenetic and FISH analysis to identify high-risk patients who may benefit from novel treatments, but such facilities are not widely available. The International Scoring System (ISS) using beta-2-microglobulin and albumin remains a widely used prognostic scoring system in many clinical practices; however it is not useful in predicting response to treatment in MM...
December 2017: BBA Clinical
https://www.readbyqxmd.com/read/28725322/recurrent-body-rash-warranted-second-desensitization-with-acyclovir-in-a-myeloma-patient-a-case-report
#5
Jack T Seki, Pamela Ng, Wallace Lam, Julie Cote, Anca Prica
A 75-year-old woman developed a moderately severe rash about a week and a half after the start of bortezomib (Btb)-based chemotherapy for IgG lambda multiple myeloma; at the time, she was also receiving acyclovir as antiviral prophylaxis in addition to herpes zoster (HZ) vaccination. HZ reactivation rate is high in Btb recipients; therefore, the timing of antiviral prevention is critical in relation to Btb. Attempts were made to identify the offending agent based on the timing of drugs administered and the appearance of skin lesions in relation to other drugs...
August 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28723635/meta-analysis-of-the-efficacy-of-treatments-for-newly-diagnosed-and-relapsed-refractory-multiple-myeloma-with-del-17p
#6
Jinghua Liu, Hui Yang, Xiaochan Liang, Yuxin Wang, Jian Hou, Yanqin Liu, Jigang Wang, Fan Zhou
We analyzed the treatment of newly diagnosed and relapsed/refractory multiple myeloma (NDMM/RRMM) patients with del(17p). Thirteen prospective studies that evaluated 3,187 MM patients, including 685with del(17p), were included in our meta-analysis. The incidence of del(17p) in NDMM and RRMM patients was similar (13% vs. 14%, respectively, P = 0.64, I2 = 94%). The overall response rate (ORR) to new agents was 40.5% and 67.1%, respectively, in RRMM patients with or without del(17p) (P = 0.1, I2 = 63.9%). NDMM patients with del(17p) treated with PAD (bortezomib, adriamycin, and dexamethasone) induction therapy followed by bortezomib maintenance therapy had higher progression-free survival (PFS) (25...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28708596/hdac6-inhibitor-wt161-downregulates-growth-factor-receptors-in-breast-cancer
#7
Teru Hideshima, Ralph Mazitschek, Jun Qi, Naoya Mimura, Jen-Chieh Tseng, Andrew L Kung, James E Bradner, Kenneth C Anderson
We have shown that WT-161, a histone deacetylase 6 (HDAC6) inhibitor, shows remarkable anti-tumor activity in multiple myeloma (MM) in preclinical models. However, its activity in other type of cancers has not yet been shown. In this study, we further evaluated the biologic sequelae of WT161 in breast cancer cell lines. WT161 triggers apoptotic cell death in MCF7, T47D, BT474, and MDA-MB231 cells, associated with decreased expression of EGFR, HER2, and ERα and downstream signaling. However, HDAC6 knockdown shows that cytotoxicity and destabilization of these receptors triggered by WT161 are not dependent on HDAC6 inhibition...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28706008/efficacy-and-safety-of-bortezomib-maintenance-in-patients-with-newly-diagnosed-multiple-myeloma-a-meta-analysis
#8
Chun-Yan Sun, Jun-Ying Li, Zhang-Bo Chu, Lu Zhang, Lei Chen, Yu Hu
Multiple myeloma (MM) is a B-cell neoplasm with a high incidence of relapse. Bortezomib has been extensively studied for the maintenance treatment of MM. Here we carried out a meta-analysis to determine the efficacy and safety of maintenance therapy with bortezomib. We searched for clinical trials in PubMed (Medline), Embase (OVID) and the Cochrane Library. Two randomized controlled trials (RCTs) enrolling a total of 1338 patients were included. Bortezomib maintenance statistically significantly improved both PFS (HR 0...
July 13, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28696369/2-5-dihydroxyacetophenone-induces-apoptosis-of-multiple-myeloma-cells-by-regulating-the-mapk-activation-pathway
#9
Jeong-Hyeon Ko, Jae Hwi Lee, Sang Hoon Jung, Seok-Geun Lee, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Woong Mo Yang, Jae-Young Um, Gautam Sethi, Kwang Seok Ahn
2,5-Dihydroxyacetophenone (DHAP) is an active compound obtained from Radix rehmanniae preparata, which is widely used as a herbal medicine in many Asian countries. DHAP has been found to possess anti-inflammatory, anti-anxiety, and neuroprotective qualities. For the present study, we evaluated the anti-cancer effects of DHAP on multiple myeloma cells. It was discovered that DHAP downregulated the expression of oncogenic gene products like Bcl-xl, Bcl-2, Mcl-1, Survivin, Cyclin D1, IAP-1, Cyclin E, COX-2, and MMP-9, and upregulated the expression of Bax and p21 proteins, consistent with the induction of G2/M phase cell cycle arrest and apoptosis in U266 cells...
July 11, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28693058/-a-prospective-multi-center-trial-of-non-interventional-and-observational-study-of-lenalidomide-in-chinese-patients-with-multiple-myeloma
#10
G M Wang, G Z Yang, Z X Huang, Y P Zhong, F Y Jin, A J Liao, X M Wang, Z Z Fu, H Liu, X L Li, J F Zhou, X Zhang, Y Hu, F Y Meng, X J Huang, W M Chen, J Lu
Objective: To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM). Methods: It was a prospective, multi-center, observational study. A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015. Relevant information was recorded, such as baseline clinical data, cytogenetic abnormalities, treatment regimens, and duration of treatment, safety, and survival...
July 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28691553/the-adverse-effect-of-fopnl-genomic-variant-is-reversed-by-bortezomib-based-treatment-protocols-in-multiple-myeloma
#11
Katalin Piroska Kiss, Gergely Varga, Gabor Mikala, Katalin Balassa, Andras Bors, Petra Kovy, Nora Meggyesi, Andras Kozma, Otto Csacsovszki, Peter Remenyi, Istvan Valyi-Nagy, Attila Tordai, Tamas Masszi, Hajnalka Andrikovics
Fibroblast growth factor receptor 1 oncogene partner N-terminal like gene (FOPNL) rs72773978 polymorphism was identified as an adverse prognostic factor in multiple myeloma (MM). We aimed to investigate the associations of rs72773978 with clinical characteristics and treatment outcome in 373 Hungarian MM patients. In our cohort, FOPNL polymorphism showed differential prognostic effect that depended on the treatment applied. Among patients treated with non-proteasome inhibitor (PI)-based therapy, carriership of the minor allele was significantly associated with adverse overall survival (p=...
July 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28686535/prospective-evaluation-of-magnetic-resonance-imaging-and-18-f-fluorodeoxyglucose-positron-emission-tomography-computed-tomography-at-diagnosis-and-before-maintenance-therapy-in-symptomatic-patients-with-multiple-myeloma-included-in-the-ifm-dfci-2009-trial-results
#12
Philippe Moreau, Michel Attal, Denis Caillot, Margaret Macro, Lionel Karlin, Laurent Garderet, Thierry Facon, Lotfi Benboubker, Martine Escoffre-Barbe, Anne-Marie Stoppa, Kamel Laribi, Cyrille Hulin, Aurore Perrot, Gerald Marit, Jean-Richard Eveillard, Florence Caillon, Caroline Bodet-Milin, Brigitte Pegourie, Veronique Dorvaux, Carine Chaleteix, Kenneth Anderson, Paul Richardson, Nikhil C Munshi, Herve Avet-Loiseau, Aurelie Gaultier, Jean-Michel Nguyen, Benoit Dupas, Eric Frampas, Françoise Kraeber-Bodere
Purpose Magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) are important imaging techniques in multiple myeloma (MM). We conducted a prospective trial in patients with MM aimed at comparing MRI and PET-CT with respect to the detection of bone lesions at diagnosis and the prognostic value of the techniques. Patients and Methods One hundred thirty-four patients received a combination of lenalidomide, bortezomib, and dexamethasone (RVD) with or without autologous stem-cell transplantation, followed by lenalidomide maintenance...
July 7, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28685863/efficacy-and-tolerability-of-the-histone-deacetylase-inhibitor-panobinostat-in-clinical-practice
#13
Marc-Andrea Baertsch, Jens Hillengass, Joanna Blocka, Stefan Schönland, Ute Hegenbart, Hartmut Goldschmidt, Marc S Raab
The histone deacetylase inhibitor panobinostat has shown efficacy in phase-II and phase-III trials for multiple myeloma and has recently received market approval in combination with bortezomib and dexamethasone. Here, we retrospectively report our single center experience with panobinostat/bortezomib/dexamethasone (FVD) in a heavily pretreated patient population (n = 24) with a high degree of refractoriness to proteasome inhibitors (PI) and immunomodulatory drugs (IMiD). Median age was 67 years (range 49-87) and the median number of prior therapies was 5 (range 2-17)...
July 7, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28684537/pomalidomide-bortezomib-and-dexamethasone-pvd-for-patients-with-relapsed-lenalidomide-refractory-multiple-myeloma
#14
Jonas Paludo, Joseph R Mikhael, Betsy R LaPlant, Alese E Halvorson, Shaji Kumar, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Angela Dispenzieri, John A Lust, Prashant Kapoor, Nelson Leung, Stephen J Russell, David Dingli, Ronald S Go, Yi Lin, Wilson I Gonsalves, Rafael Fonseca, P Leif Bergsagel, Vivek Roy, Taimur Sher, Asher A Chanan-Khan, Sikander Ailawadhi, A Keith Stewart, Craig B Reeder, Paul G Richardson, S Vincent Rajkumar, Martha Q Lacy
This phase I/II trial evaluated the maximum tolerated doses (MTD), safety and efficacy of pomalidomide, bortezomib and dexamethasone (PVD) combination in patients with relapsed, lenalidomide refractory, MM. In the phase I, dose level 1 consisted of pomalidomide 4mg PO days 1-21, bortezomib 1.0 mg/m(2) IV or SQ days 1,8,15,22 and dexamethasone 40mg PO days 1,8,15,22 given every 28 days. Bortezomib was increased to 1.3 mg/m(2) for dose level 2 and adopted in the phase 2 expansion cohort. We describe the results of 50 patients...
July 6, 2017: Blood
https://www.readbyqxmd.com/read/28684379/pharmacokinetics-directed-intravenous-busulfan-combined-with-high-dose-melphalan-and-bortezomib-as-a-conditioning-regimen-for-patients-with-multiple-myeloma
#15
Stefan K Barta, Rishi Jain, Amithaba Mazumder, Jason Carter, Lawrence Almanzar, Roy Browne, Samira Shahnaz, Richard Elkind, David Kaminetzky, Ramakrishna Battini, Olga Derman, Noah Kornblum, Amit Verma, Ira Braunschweig
BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has a well-established role in the treatment of patients with multiple myeloma. Melphalan 200 mg/m(2) (Mel200) is the most commonly used preparative regimen. Several studies have provided evidence for potential synergism and safety when combining bortezomib (Btz) or busulfan (Bu) with melphalan (Mel). PATIENTS AND METHODS: We conducted a prospective phase II study to investigate the safety and efficacy of conditioning with pharmacokinetics (PK)-directed intravenous (IV) Bu with Btz and Mel...
June 17, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28681529/targeting-complete-response-with-upfront-bortezomib-consolidation-versus-observation-after-the-achievement-of-complete-response-following-autologous-transplantation-for-multiple-myeloma-tuba-study
#16
Hideki Nakasone, Kiriko Terasako-Saito, Teiichi Hirano, Atsushi Wake, Seiichi Shimizu, Naoki Kurita, Etsuko Yamazaki, Kensuke Usuki, Kohei Akazawa, Junya Kanda, Koichiro Minauchi, Go Yamamoto, Shiori Tanimoto, Masaharu Kamoshita, Yasuhisa Yokoyama, Etsuo Miyaoka, Shuichi Ota, Shinichi Kako, Koji Izutsu, Yoshinobu Kanda
Complete response (CR) after treatment for multiple myeloma is associated with superior progression-free survival (PFS). Multiple myeloma patients were prospectively recruited for induction treatment with bortezomib and dexamethasone (BD) followed by autologous hematopoietic cell transplantation (auto-HCT) between 2010 and 2012. If patients did not achieve CR after auto-HCT, BD consolidation therapy was added to target CR. After the BD induction phase (n = 46), greater than or equal to CR was achieved in 4 patients (8%)...
July 6, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28680953/the-cost-impact-of-lenalidomide-for-newly-diagnosed-multiple-myeloma-in-the-eu5
#17
Steve Schey, Luis Felipe Casado Montero, Chloe Stengel-Tosetti, Craig J Gibson, Sujith Dhanasiri
INTRODUCTION: Lenalidomide is an active agent that was approved for use in the EU in 2015 as a first-line therapy for previously untreated, non-transplant eligible multiple myeloma patients. Our objective was to assess the cost impact of lenalidomide when selected as a first-line treatment for transplant-ineligible patients in France, Germany, Italy, Spain, and the United Kingdom (EU5). METHODS: We developed a cost-impact model of the total costs associated with newly diagnosed multiple myeloma over 5 years in the EU5 based on treatment duration and time to progression (TTP) (taken from trial data)...
2017: Oncology and Therapy
https://www.readbyqxmd.com/read/28680024/proteomic-analysis-of-serum-for-identification-of-potential-biomarkers-predicting-response-of-patients-with-refractory-multiple-myeloma-to-bortezomib%C3%A2-based-therapy
#18
Ota Fuchs
No abstract text is available yet for this article.
June 30, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28679737/how-i-treat-first-relapse-of-myeloma
#19
Jean Luc Harousseau, Michel Attal
The standard treatment of relapsed multiple myeloma (MM) was either lenalidomide-dexamethasone (RD) or bortezomib-dexamethasone (VD) but it is changing rapidly for two reasons. Firstly lenalidomide and bortezomib are currently used in frontline treatment and many patients become resistant to these agents early in the course of their disease. Secondly six second-line new agents have been recently developed and offer new possibilities (pomalidomide, carfilzomib and ixazomib, panobinostat, elotuzumab and daratumumab)...
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28679329/autoantibodies-against-%C3%AE-1-adrenergic-receptor-response-to-induction-therapy-with-bortezomib-containing-regimens-for-multiple-myeloma-patients
#20
Wen Gao, Wen-Jia Guo, Dong-Yan Hou, Guang-Zhong Yang, Yin Wu, Yan-Chen Li, Yun Leng, Yu Tang, Lin Xu, Jia-Mei Liu, Hua Wang, Xin Wang, Juan Zhang, Wen-Shu Zhao, Wen-Ming Chen, Lin Zhang
This study aims to investigate the predictive value of pre-chemotherapy β1R-AABs by evaluating the response of newly diagnosed symptomatic multiple myeloma (MM) patients to their treatment with a bortezomib-containing regimen. Forty-five de novo MM patients and 50 normal controls (NCs) were prospectively enrolled in this study. Serum titers of β1R-AABs were detected by ELISA. These 45 MM patients were divided into two groups (positive and negative groups) according to their β1R-AABs. Follow-up examinations were performed on these patients during chemotherapy induction...
July 6, 2017: Leukemia & Lymphoma
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