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Multiple Myeloma, Bortezomib

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https://www.readbyqxmd.com/read/29218097/histone-deacetylase-inhibitor-nabut-suppresses-cell-proliferation-and-induces-apoptosis-by-targeting-p21-in-multiple-myeloma
#1
Ruosi Yao, Danyang Han, Xiaoyang Sun, Chunling Fu, Qingyun Wu, Yao Yao, Hujun Li, Zhenyu Li, Kailin Xu
Multiple myeloma (MM) is an extremely serious hematological malignancy that remains incurable due to chemotherapy resistance. Epigenetic regulation is closely associated with progression of MM. Histone deacetylase inhibitor NaBut functions in various physiologic processes, including inflammation and differentiation. Its' possible roles in MM progression have not been explored. In this report, NaBut decreased survival of several human MM cell lines in a dose- and time-dependent manner. NaBut could also lead to cell cycle arrest at the G2/M phase in a dose-dependent manner...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29217780/from-transplant-to-novel-cellular-therapies-in-multiple-myeloma-emn-guidelines-and-future-perspectives
#2
Francesca Gay, Monika Engelhardt, Evangelos Terpos, Ralph Wäsch, Luisa Giaccone, Holger W Auner, Jo Caers, Martin Gramatzki, Niels van de Donk, Stefania Oliva, Elena Zamagni, Laurent Garderet, Christian Straka, Roman Hajek, Heinz Ludwig, Hermann Einsele, Meletios Dimopoulos, Mario Boccadoro, Nicolaus Kröger, Michele Cavo, Hartmut Goldschmidt, Benedetto Bruno, Pieter Sonneveld
Survival of myeloma patients has greatly improved with the use of autologous stem cell transplantation and novel agents, such as proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. Compared to bortezomib- and lenalidomide-based regimens alone, the addition of high-dose melphalan followed by autologous transplantation significantly improves progression-free survival; although an overall survival benefit was not observed in all trials. Moreover, follow-up of recent trials is still too short to show any difference in survival...
December 7, 2017: Haematologica
https://www.readbyqxmd.com/read/29212974/-ige-%C3%AE%C2%BA-type-multiple-myeloma-achieving-complete-response-with-novel-agents
#3
Tomomi Takei, Tadao Ishida, Masahiro Ikeda, Sumito Shingaki, Kanji Miyazaki, Yumiko Yoshiki, Yu Abe, Kiyoshi Okazuka, Seiko Iki, Nobuhiro Tsukada, Kenshi Suzuki
IgE multiple myeloma (MM) is a rare subtype of MM characterized by an aggressive and poor prognosis. Although novel agents have improved the prognosis of MM, there are few case reports of IgE MM treated with these agents. A 53-year-old male patient presented with pain in the right rib and was diagnosed with IgE-κ MM. He was treated with multidrug chemotherapy, including bortezomib and lenalidomide, and underwent autologous stem-cell transplantation (ASCT). Finally, he achieved a complete response after the initiation of pomalidomide...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29209721/effect-of-high-cutoff-hemodialysis-vs-conventional-hemodialysis-on-hemodialysis-independence-among-patients-with-myeloma-cast-nephropathy-a-randomized-clinical-trial
#4
Frank Bridoux, Pierre-Louis Carron, Brigitte Pegourie, Eric Alamartine, Karine Augeul-Meunier, Alexandre Karras, Bertrand Joly, Marie-Noëlle Peraldi, Bertrand Arnulf, Cécile Vigneau, Thierry Lamy, Alain Wynckel, Brigitte Kolb, Bruno Royer, Nolwenn Rabot, Lotfi Benboubker, Christian Combe, Arnaud Jaccard, Bruno Moulin, Bertrand Knebelmann, Sylvie Chevret, Jean-Paul Fermand
Importance: Cast nephropathy is the main cause of acute kidney injury in multiple myeloma and persistent reduction in kidney function strongly affects prognosis. Strategies to rapidly remove nephrotoxic serum-free light chains combined with novel antimyeloma agents have not been evaluated prospectively. Objective: To compare the hemodialysis independence rate among patients newly diagnosed with myeloma cast nephropathy treated with hemodialysis using a high-cutoff dialyzer (with very large membrane pores and high permeability to immunoglobulin light chains) or a conventional high-flux dialyzer (with small pores and lower permeability)...
December 5, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29199718/multiple-myeloma-experience-of-an-institute-in-limited-resource-setting
#5
Linu Abraham Jacob, M C Suresh Babu, K C Lakshmaiah, K Govind Babu, D Lokanatha, L K Rajeev, K N Lokesh, A H Rudresha, Ankit Agarwal, Sunny Garg
INTRODUCTION: Multiple myeloma (MM) is a plasma cell dyscrasias and an incurable clonal B-cell malignancy, with an annual incidence of 1% of all malignancies. The mainstay of treatment of myeloma is induction treatment followed by consolidation with autologous stem cell transplant (ASCT). However, still in a developing country like India where affordability is a major hurdle for health care, a number of MM patients are not able to undergo ASCT. AIM: To study the epidemiological features and outcome of MM patients treated in a limited resource setting...
January 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29196868/the-proteasome-and-proteasome-inhibitors-in-multiple-myeloma
#6
Sara Gandolfi, Jacob P Laubach, Teru Hideshima, Dharminder Chauhan, Kenneth C Anderson, Paul G Richardson
Proteasome inhibitors are one of the most important classes of agents to have emerged for the treatment of multiple myeloma in the past two decades, and now form one of the backbones of treatment. Three agents in this class have been approved by the United States Food and Drug Administration-the first-in-class compound bortezomib, the second-generation agent carfilzomib, and the first oral proteasome inhibitor, ixazomib. The success of this class of agents is due to the exquisite sensitivity of myeloma cells to the inhibition of the 26S proteasome, which plays a critical role in the pathogenesis and proliferation of the disease...
December 2, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29196043/enhancing-proteasome-inhibitory-activity-and-specificity-of-bortezomib-by-cd38-targeted-nanoparticles-in-multiple-myeloma
#7
Pilar de la Puente, Micah J Luderer, Cinzia Federico, Abbey Jin, Rebecca C Gilson, Christopher Egbulefu, Kinan Alhallak, Shruti Shah, Barbara Muz, Jennifer Sun, Justin King, Daniel Kohnen, Noha Nabil Salama, Samuel Achilefu, Ravi Vij, Abdel Kareem Azab
The establishment of more effective treatments that can circumvent chemoresistance in Multiple Myeloma (MM) is a priority. Although bortezomib (BTZ) is one of the most potent proteasome inhibitors available, still possesses limitations related to dose limiting side effects. Several strategies have been developed to improve the delivery of chemotherapies to MM by targeting different moieties expressed on MM cells to nanoparticle delivery systems (NPs), which have failed mainly due to their heterogeneous expression on these cells...
November 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29192015/the-european-medicines-agency-review-of-panobinostat-farydak-for-the-treatment-of-adult-patients-with-relapsed-and-or-refractory-multiple-myeloma
#8
REVIEW
Kyriaki Tzogani, Paula van Hennik, Ita Walsh, Pieter De Graeff, Annika Folin, Jan Sjöberg, Tomas Salmonson, Jonas Bergh, Edward Laane, Heinz Ludwig, Christian Gisselbrecht, Francesco Pignatti
On August 28, 2015, a marketing authorization valid through the European Union was issued for panobinostat, in combination with bortezomib and dexamethasone, for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD).Panobinostat is an orally available histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDAC proteins at nanomolar concentrations. HDAC proteins catalyze the removal of acetyl groups from the lysine residues of histones and some nonhistone proteins...
November 30, 2017: Oncologist
https://www.readbyqxmd.com/read/29179894/-preventative-and-therapeutic-relapse-strategies-after-allogeneic-hematopoietic-stem-cell-transplantation-guidelines-from-the-francophone-society-of-bone-marrow-transplantation-and-cellular-therapy-sfgm-tc
#9
Nabil Yafour, Florence Beckerich, Claude Eric Bulabois, Patrice Chevallier, Étienne Daguindau, Cécile Dumesnil, Thierry Guillaume, Anne Huynh, Stavroula Masouridi Levrat, Anne-Lise Menard, Mauricette Michallet, Cécile Pautas, Xavier Poiré, Aurelie Ravinet, Ibrahim Yakoub-Agha, Ali Bazarbachi
Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT). The risk of recurrence is elevated in patients with high-risk cytogenetic or molecular abnormalities, as well as when allo-HCT is performed in patients with refractory disease or with persistent molecular or radiological (PET-CT scan) residual disease. Within the frame of the 7th annual workshops of the francophone society for bone marrow transplantation and cellular therapy, the working group reviewed the literature in order to elaborate unified guidelines for the prevention and treatment of relapse after allo-HCT...
November 24, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29172760/adjusted-comparison-of-daratumumab-monotherapy-versus-real-world-historical-control-data-from-the-czech-republic-in-heavily-pretreated-and-highly-refractory-multiple-myeloma-patients
#10
Tomáš Jelínek, Vladimír Maisnar, Luděk Pour, Ivan Špička, Jiří Minařík, Evžen Gregora, Petr Kessler, Michal Sýkora, Hana Fraňková, Dagmar Adamová, Marek Wróbel, Peter Mikula, Jiří Jarkovský, Joris Diels, Xenia Gatopoulou, Šárka Veselá, Hervé Besson, Lucie Brožová, Tetsuro Ito, Roman Hájek
OBJECTIVES: We conducted an adjusted comparison of progression-free survival (PFS) and overall survival (OS) for daratumumab monotherapy versus standard of care, as observed in a real-world historical cohort of heavily pretreated multiple myeloma patients from Czech Republic. METHODS: Using longitudinal chart data from the Registry of Monoclonal Gammopathies (RMG) of the Czech Myeloma Group, patient-level data from the RMG were pooled with pivotal daratumumab monotherapy studies (GEN501 and SIRIUS; 16 mg/kg)...
November 25, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29169873/modified-hypercvad-versus-bortezomib-hypercad-in-patients-with-relapsed-refractory-multiple-myeloma
#11
Megan M Saraceni, Emma Scott, Richard T Maziarz, Matthew B Siegel, Solange Bassale, Susie Jiing, Eva Medvedova
INTRODUCTION: Multiple myeloma (MM) is an incurable plasma cell malignancy, in which aggressive relapses might require salvage cytotoxic infusional chemotherapy. Several clinical trials that reported the efficacy of bortezomib led to institutional practice changes in which vincristine was replaced with bortezomib in the modified hyperCVAD regimen, creating a new treatment regimen, named "bortezomib-hyperCAD." PATIENTS AND METHODS: We retrospectively describe the effectiveness and tolerability of 2 chemotherapy regimens among 33 patients with relapsed and/or refractory MM...
November 2, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29166734/-a-retrospective-study-of-the-bird-regimen-in-the-treatment-of-relapsed-refractory-multiple-myeloma
#12
X L Liu, L Li, Q L Shi, L J Chen, X X Cao, J Li, A J Liao, D H Zou, J N Sun, S J Gao, W Li, J Hou, F Y Jin
Objective: To evaluate efficacy of the BiRd regimen, a combination of clarithromycin, lenalidomide, and dexamethasone, in the treatment of patients with relapsed/refractory multiple myeloma (RRMM) . Methods: Patients with RRMM treated with BiRd between September 11, 2013 and August 1, 2016 at six centers were included to evaluate overall survival rate (ORR) , clinical benefit rate (CBR) , progression-free survival (PFS) , overall survival (OS) , as well as adverse events. Results: Of 30 patients with RRMM, 27 patients were evaluable, and ORR and CBR were 51...
October 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29164606/safety-and-efficacy-of-pomalidomide-dexamethasone-and-pegylated-liposomal-doxorubicin-for-patients-with-relapsed-or-refractory-multiple-myeloma
#13
Alexa Cohen, Tanya M Spektor, Laura Stampleman, Alberto Bessudo, Peter J Rosen, Leonard M Klein, Thomas Woliver, Marshall Flam, Shahrooz Eshaghian, Youram Nassir, Tina Maluso, Regina A Swift, Robert Vescio, James R Berenson
Immunomodulatory drugs including thalidomide, lenalidomide (LEN) and pomalidomide (POM), are effective for treating multiple myeloma (MM). POM has shown enhanced efficacy with dexamethasone (DEX). Pegylated liposomal doxorubicin (PLD) with bortezomib is US Food and Drug Administration-approved for treating MM. PLD with LEN or thalidomide has shown efficacy for MM patients. LEN with DEX, PLD and bortezomib achieves high response rates. We evaluated the combination of POM with DEX 40 mg and PLD 5 mg/m(2) with the latter two drugs administered on days 1, 4, 8 and 11 on a 28-day cycle for the treatment of relapsed/refractory MM patients...
November 21, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29157092/single-agent-and-synergistic-combinatorial-efficacy-of-first-in-class-small-molecule-imipridone-onc201-in-hematological-malignancies
#14
Varun V Prabhu, Mala K Talekar, Amriti R Lulla, C Leah B Kline, Lanlan Zhou, Junior Hall, A Pieter J Van den Heuvel, David T Dicker, Jawad Babar, Stephan A Grupp, Mathew J Garnett, Ultan McDermott, Cyril H Benes, Jeffrey J Pu, David F Claxton, Nadia Khan, Wolfgang Oster, Joshua E Allen, Wafik S El-Deiry
ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1-8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL), cutaneous T-cell lymphoma (CTCL), Hodgkin's lymphoma (nodular sclerosis) and multiple myeloma (MM) cell lines including cells resistant to standard of care (dexamethasone in MM) and primary samples...
November 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29151530/successful-autologous-hematopoietic-stem-cell-transplantation-followed-by-bortezomib-maintenance-in-a-patient-with-relapsed-cd138-low-multiple-solitary-plasmacytomas-harboring-a-17p-deletion
#15
Hiroaki Kitamura, Yasushi Kubota, Kyosuke Yamaguchi, Kazuharu Kamachi, Atsujiro Nishioka, Masako Yokoo, Takero Shindo, Toshihiko Ando, Kensuke Kojima, Shinya Kimura
Solitary plasmacytoma of bone (SBP) tends to progress to multiple myeloma (MM); however, progression to multiple solitary plasmacytomas (MSP) is rare. We report a case of CD138-low MSP with 17p deletion in a patient with relapsed SBP. 17p deletion is associated with a poor outcome in patients with MM, and the low expression of CD138 in myeloma cells is associated with drug resistance and a poor prognosis. The patient was successfully treated with bortezomib plus dexamethasone induction therapy and autologous hematopoietic stem cell transplantation followed by bortezomib maintenance therapy...
November 20, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29150421/final-analysis-of-survival-outcomes-in-the-randomized-phase-3-first-trial
#16
Thierry Facon, Meletios A Dimopoulos, Angela Dispenzieri, John V Catalano, Andrew Belch, Michele Cavo, Antonello Pinto, Katja Weisel, Heinz Ludwig, Nizar J Bahlis, Anne Banos, Mourad Tiab, Michel Delforge, Jamie D Cavenagh, Catarina Geraldes, Je-Jung Lee, Christine Chen, Albert Oriol, Javier De La Rubia, Darell White, Daniel Binder, Jin Lu, Kenneth C Anderson, Philippe Moreau, Michel Attal, Aurore Perrot, Bertrand Arnulf, Lugui Qiu, Murielle Roussel, Eileen Boyle, Salomon Manier, Mohamad Mohty, Herve Avet-Loiseau, Xavier Leleu, Annette Ervin-Haynes, Guang Chen, Vanessa Houck, Lotfi Benboubker, Cyrille Hulin
This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥ 60 months' follow-up)...
November 17, 2017: Blood
https://www.readbyqxmd.com/read/29127588/daratumumab-a-review-in-relapsed-and-or-refractory-multiple-myeloma
#17
Hannah A Blair
Intravenous daratumumab (DARZALEX®) is a first-in-class human IgG1κ monoclonal antibody against CD38 available for use in patients with relapsed and/or refractory multiple myeloma. In phase I/II and II trials and a pooled analysis of these studies, daratumumab monotherapy induced an overall response (partial response or better) in approximately one-third of patients; responses were rapid, deep and durable. An overall survival (OS) benefit was seen with daratumumab monotherapy, including in patients with a minimal response or stable disease...
November 10, 2017: Drugs
https://www.readbyqxmd.com/read/29122646/drug-response-prediction-in-high-risk-multiple-myeloma
#18
A J Vangsted, S Helm-Petersen, J B Cowland, P B Jensen, P Gimsing, B Barlogie, S Knudsen
A Drug Response Prediction (DRP) score was developed based on gene expression profiling (GEP) from cell lines and tumor samples. Twenty percent of high-risk patients by GEP70 treated in Total Therapy 2 and 3A have a progression-free survival (PFS) of more than 10years. We used available GEP data from high-risk patients by GEP70 at diagnosis from Total Therapy 2 and 3A to predict the response by the DRP score of drugs used in the treatment of myeloma patients. The DRP score stratified patients further. High-risk myeloma with a predicted sensitivity to melphalan by the DRP score had a prolonged PFS, HR=2...
November 6, 2017: Gene
https://www.readbyqxmd.com/read/29113288/hdac6-inhibitor-wt161-downregulates-growth-factor-receptors-in-breast-cancer
#19
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...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29110190/pomalidomide-a-review-in-relapsed-and-refractory-multiple-myeloma
#20
Sheridan M Hoy
Pomalidomide (Imnovid(®); Pomalyst(®)), an analogue of thalidomide, is an immunomodulatory agent, with several mechanisms of action (both direct and indirect) thought to be involved in its anti-myeloma activity. Oral pomalidomide is available in several countries for use in combination with low-dose dexamethasone in adults with relapsed and refractory multiple myeloma. In multinational, phase II or III studies in patients with refractory, or relapsed and refractory multiple myeloma who had received ≥ 2 prior treatment regimens (including ≥ 2 cycles of both lenalidomide and bortezomib), pomalidomide plus low-dose dexamethasone was associated with prolonged progression-free survival (PFS) and overall survival and an improved overall response rate...
November 2017: Drugs
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