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Multiple Myeloma, Bortezomib

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https://www.readbyqxmd.com/read/28534173/successful-treatment-of-patients-with-newly-diagnosed-untreated-light-chain-multiple-myeloma-with-a-combination-of-bendamustine-prednisone-and-bortezomib-bpv
#1
Hannah Tessenow, Madlen Holzvogt, Bruno Holzvogt, Marc Andrea, Simone Heyn, Thomas Schliwa, Maik Schwarz, Thomas Zehrfeld, Cornelia Becker, Christian Pfrepper, Georg Nikolaus Franke, Rainer Krahl, Madlen Jentzsch, Sabine Leiblein, Sebastian Schwind, Marius Bill, Vladan Vucinic, Thoralf Lange, Dietger Niederwieser, Wolfram Pönisch
INTRODUCTION: Patients with light chain myeloma frequently have a light chain tubular cast nephropathy, which can lead to severe renal impairment. In the present retrospective study, bortezomib was combined with other active substances like bendamustine and prednisone (BPV), in order to assess the efficacy and toxicity of the combination therapy in patients with light chain multiple myeloma. METHODS: Between September 2008 and May 2015, 25 patients with newly diagnosed light chain multiple myeloma were treated with bendamustine 60 mg/m(2) on days 1 and 2, bortezomib 1...
May 22, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28521480/clinical-effect-of-immunophenotyping-on-the-prognosis-of-multiple-myeloma-patients-treated-with-bortezomib
#2
Noriyoshi Iriyama, Katsuhiro Miura, Yoshihiro Hatta, Sumiko Kobayashi, Yoshihito Uchino, Daisuke Kurita, Hitomi Sakagami, Hiromichi Takahashi, Masashi Sakagami, Yujin Kobayashi, Masaru Nakagawa, Shimon Ohtake, Yoshikazu Iizuka, Masami Takei
In the present study, the effect of immunophenotyping on the prognoses of patients with multiple myeloma (MM) treated with bortezomib plus dexamethasone was investigated. The study involved 46 patients with MM, and analyzed the prognostic significance of the expression of cluster of differentiation (CD)45, CD56 and mature plasma cell (MPC)-1, and other factors including the International Staging System (ISS) stage, age, gender, the immunoglobulin subtype and the treatment line number prior to bortezomib treatment...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28509582/tariquidar-sensitizes-multiple-myeloma-cells-to-proteasome-inhibitors-via-reduction-of-hypoxia-induced-p-gp-mediated-drug-resistance
#3
Barbara Muz, Hubert D Kusdono, Feda Azab, Pilar de la Puente, Cinzia Federico, Mark Fiala, Ravi Vij, Noha N Salama, Abdel Kareem Azab
Multiple myeloma (MM) presents a poor prognosis and high lethality of patients due to development of drug resistance. P-glycoprotein (P-gp), a drug-efflux transporter, is upregulated in MM patients post-chemotherapy and is involved in the development of drug resistance since many anti-myeloma drugs (including proteasome inhibitors) are P-gp substrates. Hypoxia develops in the bone marrow niche during MM progression and has long been linked to chemoresistance. Additionally, hypoxia-inducible transcription factor (HIF-1α) was demonstrated to directly regulate P-gp expression...
May 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28508984/successful-treatment-of-myeloma-cast-nephropathy-using-bortezomib-based-chemotherapy-plus-selective-plasma-exchange
#4
Mayuko Kawabe, Izumi Yamamoto, Ai Katsuma, Naomi Hayashi, Yo Komatsuzaki, Yasuyuki Nakada, Akihiro Shimizu, Yudo Tanno, Ichiro Ohkido, Nobuo Tsuboi, Kazuhito Suzuki, Takaki Shimada, Yoji Ogasawara, Katsuki Sugiyama, Keisuke Aiba, Takashi Yokoo
Myeloma cast nephropathy is a major complication of multiple myeloma. Recent evidence has demonstrated that the earlier induction of bortezomib-based chemotherapy with plasma exchange (PE) provides better results for kidney function and patient survival. Due to its non-selectivity, PE with albumin replacement carries the risk of fibrinogen loss, leading to bleeding. We herein report a case of successful treatment of myeloma cast nephropathy using bortezomib-based chemotherapy and selective PE. A 61-year-old woman who had a 20-year history of type II diabetes mellitus was admitted to our hospital for the evaluation of hypercalcemia, severe kidney dysfunction, and anemia...
November 2016: CEN Case Reports
https://www.readbyqxmd.com/read/28504846/adverse-event-management-in-patients-with-relapsed-and-refractory-multiple-myeloma-taking-pomalidomide-plus-low-dose-dexamethasone-a-pooled-analysis
#5
Philippe Moreau, Meletios A Dimopoulos, Paul G Richardson, David S Siegel, Michele Cavo, Paolo Corradini, Katja Weisel, Michel Delforge, Peter O'Gorman, Kevin Song, Christine Chen, Nizar Bahlis, Albert Oriol, Markus Hansson, Martin Kaiser, Pekka Anttila, Reinier Raymakers, Cristina Joao, Gordon Cook, Lars Sternas, Tsvetan Biyukov, Ana Slaughter, Kevin Hong, Jennifer Herring, Xin Yu, Mohamed Zaki, Jesus San-Miguel
OBJECTIVES: Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs is important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management. METHODS: This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy...
May 15, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28500235/beta-catenin-inhibitor-bc2059-is-efficacious-as-monotherapy-or-in-combination-with-proteasome-inhibitor-bortezomib-in-multiple-myeloma
#6
Ioanna Savvidou, Tiffany Khong, Andrew Cuddihy, Catriona McLean, Stephen Horrigan, Andrew Spencer
Currently available treatment options are unlikely to be curative for the majority of multiple myeloma (MM) patients, emphasizing a continuing role for the introduction of investigational agents that can overcome drug resistance. The canonical Wnt/beta-catenin signalling pathway, essential for self-renewal, growth and survival, has been found to be dysregulated in MM, particularly in advanced stages of disease. This provides the rationale for evaluating the novel beta-catenin inhibitor BC2059 as monotherapy and in combination with proteasome inhibitors in vitro and in vivo...
May 12, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28492559/mk2206-enhances-the-cytocidal-effects-of-bufalin-in-multiple-myeloma-by-inhibiting-the-akt-mtor-pathway
#7
Ru-Fang Xiang, Yan Wang, Nan Zhang, Wen-Bin Xu, Yang Cao, Jia Tong, Jun-Min Li, Ying-Li Wu, Hua Yan
Despite the development of promising cancer therapeutic drugs, multiple myeloma (MM) remains an incurable disease. Bufalin is a bufanolide steroid compound of the traditional Chinese medicine Chan Su that was previously shown to exert growth suppression effects on myeloma cell lines. Previous studies conducted by our group demonstrated that bufalin activated the AKT/mTOR pathway in myeloma cells, which is considered an essential pathway to disease progression and is related to drug resistance in MM. In view of the significant role of AKT in MM, the allosteric AKT inhibitor MK2206 was selected in order to enhance the antitumor effects of bufalin in different MM cell lines (NCI-H929, U266, LP-1 and RPMI8226)...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28490465/dual-inhibition-of-ezh2-and-ezh1-sensitizes-prc2-dependent-tumors-to-proteasome-inhibition
#8
Ola Rizq, Naoya Mimura, Motohiko Oshima, Atsunori Saraya, Shuhei Koide, Yuko Kato, Kazumasa Aoyama, Yaeko Nakajima-Takagi, Changshan Wang, Tetsuhiro Chiba, Anqi Ma, Jian Jin, Tohru Iseki, Chiaki Nakaseko, Atsushi Iwama
<br /> <p>EZH2 and EZH1, the catalytic components of polycomb repressive complex 2 (PRC2), trigger trimethylation of H3K27 (H3K27me3) to repress the transcription of target genes and are implicated in the pathogenesis of various cancers including multiple myeloma (MM) and prostate cancer. Here, we investigated the preclinical effects of UNC1999, a dual inhibitor of EZH2 and EZH1, in combination with proteasome inhibitors on MM and prostate cancer.</p> <br /><br />Experimental Design: <br /> <p>In vitro and in vivo efficacy of UNC1999 and the combination with proteasome inhibitors was evaluated in MM cell lines, primary patient cells and in a xenograft model...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28487944/bortezomib-protects-against-dextran-sulfate-sodium%C3%A2-induced-ulcerative-colitis-in-mice
#9
Li-Hong Hu, Yu-Jing Fan, Qing Li, Jing-Ming Guan, Bo Qu, Feng-Hua Pei, Bing-Rong Liu
Bortezomib, a first‑in‑class proteasome inhibitor, is a standard method of treatment in multiple myeloma. In the present study, the therapeutic effect of bortezomib was evaluated in an ulcerative colitis model induced by dextran sulfate sodium (DSS) in mice, and the mechanism of action was also investigated. Mice were administered with 3% DSS drinking water for 7 consecutive days and then they were intraperitoneally treated with bortezomib (0.2, 0.6 or 1 mg/kg) for 1, 3 or 7 days. Mice in the control group and the DSS group were provided the same volume of PBS, respectively...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28479592/a-novel-agent-sl-401-induces-anti-myeloma-activity-by-targeting-plasmacytoid-dendritic-cells-osteoclastogenesis-and-cancer-stem-like-cells
#10
A Ray, D S Das, Y Song, V Macri, P Richardson, C L Brooks, D Chauhan, K C Anderson
Novel therapies for multiple myeloma (MM) can target mechanism(s) in the host-MM bone marrow (BM) microenvironment mediating MM progression and chemoresistance. Our studies showed increased numbers of tumor-promoting, immunosuppressive, and drug-resistant plasmacytoid dendritic cells (pDCs) in the MM BM microenvironment. pDC-MM cell interactions upregulate interleukin-3 (IL-3), which stimulates both pDC survival and MM cell growth. Since IL-3R is highly expressed on pDCs in the MM BM milieu, we here targeted pDCs using a novel IL-3R-targeted therapeutic SL-401...
May 8, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28474745/daratumumab-monotherapy-compared-with-historical-control-data-in-heavily-pretreated-and-highly-refractory-patients-with-multiple-myeloma-an-adjusted-treatment-comparison
#11
Saad Z Usmani, Joris Diels, Tetsuro Ito, Maneesha Mehra, Imran Khan, Annette Lam
Daratumumab is a human CD38-directed monoclonal antibody approved in the United States as monotherapy for patients with multiple myeloma (MM) who have received ≥3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD, and in combination with lenalidomide/dexamethasone or bortezomib/dexamethasone for patients with MM who have received ≥1 prior LOT. This study compared the efficacy of daratumumab monotherapy versus historical controls through adjusted treatment comparison...
May 5, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28468087/-efficacy-and-safety-of-ctd-and-pcd-regimens-in-treatment-of-patients-with-newly-diagnosed-multiple-myeloma
#12
Y Gu, Y H Yuan, Q L Shi, X Y Qu, J Xu, R Guo, J D Xu, J Y Li, L J Chen
Objective: To observe the efficacy and safety of CTD (cyclophosphamide, thalidomide, dexamethasone) and PCD (bortezomib, cyclophosphamide, dexamethasone) regimens in treatment of patients with newly diagnosed multiple myeloma (NDMM) . Methods: A retrospective analysis was carried out on 88 cases of NDMM patients admitted to our hospital from July 2013 to January 2016, including 49 cases in CTD group and 39 cases in PCD group. The outcomes of two different regimens were analyzed, including response, prognosis, and adverse events...
April 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28467313/igg-kappa-monoclonal-gammopathy-of-unknown-significance-with-al-amyloidosis-simulating-giant-cell-arteritis
#13
V M Pompilian, S Tanaseanu, Camelia Badea, Sabina Zurac, C Socoliuc, Sorina Badelita, Elena Botez, Mihaela Antohe
Monoclonal gammopathies complicated by AL amyloidosis can mimic giant cell arteritis (GCA).We hereby present the case of a 63 year old woman in whom symptoms consistent with GCA were the first manifestations of a monoclonal gammopathy of unknown significance (MGUS) associated with amyloidosis. A 63 year old woman was admitted for temporal headache, maseterine claudication, neck and shoulder stiffness. She was recently diagnosed with carpal tunnel syndrome. On physical examination she had prominent temporal arteries, macroglosia and orthostatic hypotension...
May 3, 2017: Romanian Journal of Internal Medicine, Revue Roumaine de Médecine Interne
https://www.readbyqxmd.com/read/28466536/a-retrospective-analysis-of-3954-patients-in-phase-2-3-trials-of-bortezomib-for-the-treatment-of-multiple-myeloma-towards-providing-a-benchmark-for-the-cardiac-safety-profile-of-proteasome-inhibition-in-multiple-myeloma
#14
Jacob P Laubach, Javid J Moslehi, Sanjeev A Francis, Jesús F San Miguel, Pieter Sonneveld, Robert Z Orlowski, Philippe Moreau, Laura Rosiñol, Edward A Faber, Peter Voorhees, Maria-Victoria Mateos, Loreta Marquez, Huaibao Feng, Avinash Desai, Helgi van de Velde, Jennifer Elliott, Hongliang Shi, Edward Dow, Nishith Jobanputra, Dixie-Lee Esseltine, Liviu Niculescu, Kenneth C Anderson, Sagar Lonial, Paul G Richardson
This retrospective analysis aimed to establish the overall cardiac safety profile of bortezomib using patient-level data from one phase 2 and seven phase 3 studies in previously untreated and relapsed/refractory multiple myeloma (MM). Seven clinically relevant primary [congestive heart failure (CHF), arrhythmias, ischaemic heart disease (IHD), cardiac death] and secondary (hypertension, dyspnoea, oedema) cardiac endpoints were defined based on MedDRA v16.0 preferred terms. 2509 bortezomib-treated patients and 1445 patients in non-bortezomib-based control arms were included...
May 3, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28463768/homoharringtonine-enhances-bortezomib-antimyeloma-activity-in-myeloma-cells-adhesion-to-bone-marrow-stromal-cells-and-in-scid-mouse-xenografts
#15
Ping Chen, Qin Yuan, Hui Yang, Xiaofang Wen, Peidong You, Diyu Hou, Jieqiong Xie, Yu Cheng, Huifang Huang
Despite the great progress in the treatment, multiple myeloma (MM) still remains incurable. Bortezomib (BTZ), a reversible inhibitor of the 26S proteasome, is very effective against MM but unable to eradicate the MM cells in bone marrow niche eventually causing the disease relapse. Homoharringtonine (HHT) is a known anti-leukemia drug that inhibits MM both in vitro and in vivo. This study aimed to investigate whether HHT could potentiate the anti-tumor activity of BTZ in MM cells cocultured with bone marrow stromal cells and in vivo xenograft models...
April 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28455955/sphingosine-kinase-2-and-multiple-myeloma
#16
Nigel J Pyne, Susan Pyne
News on: Sphingosine kinase 2 inhibition synergises with bortezomib to target myeloma by enhancing endoplasmic reticulum stress, by Wallington-Beddoe et al. Oncotarget. 2017; doi: 10.18632/oncotarget.17115.
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28455546/safety-of-btz-retreatment-for-patients-with-low-grade-peripheral-neuropathy-during-the-initial-treatment
#17
Aleksandra P Vidisheva, James Wang, Tanya M Spektor, Jacob D Bitran, Jose Lutzky, Imad A Tabbara, Joseph Z Ye, Sikander Ailawadhi, Laura V Stampleman, Ronald G Steis, Mehdi M Moezi, Regina A Swift, Tina M Maluso, Kyle A Udd, Shahrooz Eshaghian, Youram Nassir, James R Berenson
OBJECTIVE: Neuropathy is an important complication that may limit treatment options for patients with multiple myeloma. Previous studies have focused on treatment efficacy and have shown that retreatment with bortezomib (BTZ) is an effective treatment option. The goal of this study was to focus on the clinical manifestations of peripheral neuropathy (PN) and to retrospectively compare the incidence and severity of PN between the initial BTZ regimen and upon retreatment. Furthermore, this study evaluated how certain factors affect BIPN, which will help determine what conditions should be considered prior to retreatment...
April 28, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28454444/anterior-mediastinum-invasion-by-multiple-myeloma-a-case-report
#18
Ying-Hui Xu, Lu-Guo Sun, Chao Sun, Ou Bai, Ting-Ting Liang, Ke-Wei Ma
Multiple myeloma (MM) is a clonal proliferation of malignant plasma cells in the bone marrow (BM) that secretes monoclonal paraproteins in the blood serum and urine. Bone marrow MM cells can invade and damage the functions of other tissues and organs, such as the lungs, spleen, liver, pancreas, kidneys and lymph nodes. However, the invasion of MM cells primarily located in the BM to the anterior mediastinum at the site of the thymus is an extremely rare event. The current study reports the case of a 53-year-old female who presented with MM with involvement of the anterior mediastinum...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28450863/the-proteasome-inhibitor-bortezomib-controls-indoleamine-2-3-dioxygenase-1-breakdown-and-restores-immune-regulation-in-autoimmune-diabetes
#19
Giada Mondanelli, Elisa Albini, Maria T Pallotta, Claudia Volpi, Lucienne Chatenoud, Chantal Kuhn, Francesca Fallarino, Davide Matino, Maria L Belladonna, Roberta Bianchi, Carmine Vacca, Silvio Bicciato, Louis Boon, Giovanni Ricci, Ursula Grohmann, Paolo Puccetti, Ciriana Orabona
Bortezomib (BTZ) is a first-in-class proteasome inhibitor approved for the therapy of multiple myeloma that also displays unique regulatory activities on immune cells. The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan metabolizing enzyme exerting potent immunoregulatory effects when expressed in dendritic cells (DCs), the most potent antigen-presenting cells capable of promoting either immunity or tolerance. We previously demonstrated that, in inflammatory conditions, IDO1 is subjected to proteasomal degradation in DCs, turning these cells from immunoregulatory to immunostimulatory...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28448171/novel-investigational-drugs-active-as-single-agents-in-multiple-myeloma
#20
Mattia D'Agostino, Marco Salvini, Antonio Palumbo, Alessandra Larocca, Francesca Gay
Multiple myeloma (MM) is a hematologic malignancy characterized by proliferation of malignant plasma cells. patient outcome has improved markedly over the last decades due to the introduction of novel therapeutic agents such as bortezomib, thalidomide and lenalidomide. However, MM still remains largely incurable and patients eventually become refractory to available treatments. To address this unmet medical need, a variety of new molecules are currently being developed in preclinical models and/or are being investigated in clinical studies...
May 8, 2017: Expert Opinion on Investigational Drugs
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