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https://www.readbyqxmd.com/read/27913860/improved-clinical-outcomes-for-multiple-myeloma-patients-treated-at-a-single-specialty-clinic
#1
Ariana Berenson, Suzie Vardanyan, Michael David, James Wang, Nika Manik Harutyunyan, Jillian Gottlieb, Ran Halleluyan, Tanya M Spektor, Kyle A Udd, Shahrooz Eshaghian, Youram Nassir, Benjamin Eades, Regina Swift, James R Berenson
Despite recent advances made in its treatment, multiple myeloma (MM) remains an incurable B cell malignancy. Thus, the objective for treating these patients is to prolong overall survival (OS) and preserve patients' quality of life. We have analyzed data from 264 consecutive MM patients who had their initial visit between July 1, 2004 and December 1, 2014 and have received treatment in a single clinic specializing in MM. We determined their progression-free survival (PFS, OS, and 5-year OS). The PFS for frontline (n = 165 treatments), salvage (n = 980), and all treatments (n = 1145) were 13...
December 2, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#2
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913523/advances-and-practical-use-of-monoclonal-antibodies-in-multiple-myeloma-therapy
#3
Hans C Lee, Donna M Weber
The use of proteasome inhibitors and immunomodulatory agents in the treatment of myeloma have resulted in significant improvements in patient outcomes over the last decade. Although these agents now form the backbone of current myeloma treatment regimens both in the frontline and in a relapsed setting, drug resistance remains an inevitable challenge that most patients will encounter during their disease course. Hence, new treatment strategies continue to be explored, and the recent regulatory approvals of the monoclonal antibodies (mAbs) daratumumab (DARA) and elotuzumab (ELO), which target the plasma cell surface proteins CD38 and signaling lymphocytic activation molecule F7 (SLAMF7), respectively, have heralded the long-awaited era of antibody-based approaches in the treatment of myeloma...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913522/role-of-stem-cell-transplant-and-maintenance-therapy-in-plasma-cell-disorders
#4
Philip L McCarthy, Sarah A Holstein
Autologous stem cell transplant (ASCT) has been an important component of therapy for myeloma patients eligible for high-dose chemotherapy. Recent studies comparing early transplant to low-dose chemotherapy support the continued use of ASCT as consolidation following induction therapy, even in the era of immunomodulatory drugs, proteasome inhibitors, and other novel agents. Despite the marked improvements in outcomes with this approach, most patients will eventually experience disease progression. Thus, inclusion of post-ASCT consolidation/maintenance strategies is used to improve long-term disease control...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913521/sequencing-of-nontransplant-treatments-in-multiple-myeloma-patients-with-active-disease
#5
Andrew J Yee, Noopur S Raje
The approval of several different classes of drugs in recent years has resulted in a dramatic expansion of treatment options for multiple myeloma patients, improving both survival and quality of life. Lenalidomide and bortezomib are now core components of treatment both at time of diagnosis and at relapse. Next-generation immunomodulatory drugs, like pomalidomide, and newer proteasome inhibitors like carfilzomib and ixazomib are available for use at relapse. Drugs with novel mechanisms of action such as the histone deacetylase inhibitor panobinostat and the monoclonal antibodies targeting SLAMF7 (elotuzumab) and CD38 (daratumumab) are significant steps forward...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913520/myeloma-management-of-the-newly-diagnosed-high-risk-patient
#6
Angela Dispenzieri
Although there have been many definitions for high-risk (HR) myeloma, most recent consensus for classifying risk in patients with newly diagnosed multiple myeloma (NMM) comes from the International Myeloma Working Group. This recently published revised International Staging System includes del(17p) or t(4;14) by fluorescence in situ hybridization, β-2 microglobulin, albumin, and lactate dehydrogenase. These elements should be captured in all NMM patients. The optimal treatments for HR myeloma have not been fully worked out; therefore, these patients should be considered for clinical trials...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912846/new-insights-and-evolving-role-of-pegylated-liposomal-doxorubicin-in-cancer-therapy
#7
REVIEW
Alberto A Gabizon, Yogita Patil, Ninh M La-Beck
We herein review various pharmacological and clinical aspects of pegylated liposomal doxorubicin (PLD), the first nanomedicine to be approved for cancer therapy, and discuss the gap between its potent antitumor activity in preclinical studies and its comparatively modest achievements in clinical studies and limited use in clinical practice. PLD is a complex formulation of doxorubicin based on pharmaceutical nanotechnology with unique pharmacokinetic and pharmacodynamic properties. Its long circulation time with stable retention of the payload and its accumulation in tumors with high vascular permeability both result in important advantages over conventional chemotherapy...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27912844/heparanase-from-basic-research-to-therapeutic-applications-in-cancer-and-inflammation
#8
Israel Vlodavsky, Preeti Singh, Ilanit Boyango, Lilach Gutter-Kapon, Michael Elkin, Ralph D Sanderson, Neta Ilan
Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. In contrast, knockdown of heparanase or treatments of tumor-bearing mice with heparanase-inhibiting compounds, markedly attenuate tumor progression further underscoring the potential of anti-heparanase therapy for multiple types of cancer...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#9
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27910963/daratumumab-monoclonal-antibody-therapy-to-treat-multiple-myeloma
#10
C Xia, M Ribeiro, S Scott, S Lonial
Daratumumab (Darzalex[TM]) is a human monoclonal antibody (MAb) that targets CD38; a surface protein highly expressed across multiple myeloma (MM) cells. Preclinical studies have shown daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis upon secondary crosslinking and immunomodulatory effects via a decrease in immune suppressive cells. Daratumumab has a favorable toxicity profile and encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) and stem cell transplant have already failed...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27910767/immunostimulatory-effects-of-melphalan-and-usefulness-in-adoptive-cell-therapy-with-antitumor-cd4-t-cells
#11
Michal Kuczma, Zhi-Chun Ding, Gang Zhou
The alkylating agent melphalan is used in the treatment of hematological malignancies, especially multiple myeloma. In the past, the usefulness of melphalan has been solely attributed to its cytotoxicity on fastgrowing cancerous cells. Although the immunomodulatory effects of melphalan were suggested many years ago, only recently has this aspect of melphalan's activity begun to be elucidated at the molecular level. Emerging evidence indicates that melphalan can foster an immunogenic microenvironment by inducing immunogenic cell death (ICD) as characterized by membrane translocation of endoplasmic reticulum protein calreticulin (CRT) and by release of chromatin-binding protein high-mobility group box 1 (HMGB1)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27909306/rpl5-on-1p22-1-is-recurrently-deleted-in-multiple-myeloma-and-its-expression-is-linked-to-bortezomib-response
#12
I J F Hofman, M Van Duin, E De Bruyne, L Fancello, G Mulligan, E Geerdens, E Garelli, C Mancini, H Lemmens, M Delforge, P Vandenberghe, I Wlodarska, A Aspesi, L Michaux, K Vanderkerken, P Sonneveld, K De Keersmaecker
Chromosomal region 1p22 is deleted in ⩾20% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5) and ribosomal protein L5 (RPL5). Low mRNA expression of EVI5 and RPL5 was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5 and RPL5, however, 1p22 deletion status is a bad predictor of RPL5 expression in some cases, suggesting that other mechanisms downregulate RPL5 expression...
December 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27907052/prevalence-and-mortality-related-factors-of-multiple-myeloma-in-taiwan
#13
Jia-Hong Chen, Chi-Hsiang Chung, Yung-Chih Wang, Shun-Neng Hsu, Wen-Yen Huang, Wu-Chien Chien
In this retrospective cohort study based in Taiwan, we reported the current epidemiology of patients with multiple myeloma and analyzed the factors affecting mortality. We identified 7285 patients with newly diagnosed multiple myeloma (MM) between 1997 and 2013 in Taiwan. Privileges data from the National Health Institute Research Database was used, as it is made readily available to the public in electronic format for research purposes. From 1997 to 2013, the average incidence of MM per 100,000 people was 1...
2016: PloS One
https://www.readbyqxmd.com/read/27905203/efficacy-and-toxicity-of-the-combination-chemotherapy-of-thalidomide-alkylating-agent-and-steroid-for-relapsed-refractory-myeloma-patients-a-report-from-the-korean-multiple-myeloma-working-party-kmmwp-retrospective-study
#14
Jihyun Kwon, Chang-Ki Min, Kihyun Kim, Jae-Joon Han, Joon Ho Moon, Hye Jin Kang, Hyeon-Seok Eom, Min Kyoung Kim, Hyo Jung Kim, Dok Hyun Yoon, Jeong-Ok Lee, Won Sik Lee, Jae Hoon Lee, Je-Jung Lee, Yoon-Seok Choi, Sung Hyun Kim, Sung-Soo Yoon
We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35...
December 1, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27904737/a-clinical-update-on-the-role-of-carfilzomib-in-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#15
REVIEW
B Franken, N W C J van de Donk, J C Cloos, S Zweegman, H M Lokhorst
Even though the prognosis of patients with multiple myeloma is continuing to improve, all patients eventually develop relapsed refractory disease. Several novel therapeutics have been developed in the last few years including the second-generation proteasome inhibitor carfilzomib which has been approved for patients with relapsed and refractory multiple myeloma in the United States since 2012. Recently data from several phase III studies have become available showing the promising efficacy of carfilzomib in combination with lenalidomide, which led to the renewed approval of carfilzomib in combination with lenalidomide and dexamethasone for relapsed myeloma in 2015...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27903750/nuclear-export-of-ubiquitinated-proteins-determines-the-sensitivity-of-colorectal-cancer-to-proteasome-inhibitor
#16
Tingyu Wu, Wei Chen, Yongwang Zhong, Xiaodan Hou, Shengyun Fang, Chen-Ying Liu, Guanghui Wang, Tong Yu, Yu-Yang Huang, Xuesong Ouyang, Henry Q X Li, Long Cui, Yili Yang
Although proteasome inhibitors such as Bortezomib had significant therapeutic effects in multiple myeloma and mantel cell lymphoma, they exhibited minimal clinical activity as a mono-therapy for solid tumors, including colorectal cancer. We found in the present study that proteasome inhibition induced a remarkable nuclear exportation of ubiquitinated proteins. Inhibition of CRM1, the nuclear export carrier protein, hampered protein export and synergistically enhanced the cytotoxic action of Bortezomib on colon cancer cells containing wild type p53, which underwent G2/M cell cycle block and apoptosis...
November 30, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27902770/mitochondrial-targeted-decyl-triphenylphosphonium-enhances-2-deoxy-d-glucose-mediated-oxidative-stress-and-clonogenic-killing-of-multiple-myeloma-cells
#17
Jeanine Schibler, Ann M Tomanek-Chalkley, Jessica L Reedy, Fenghuang Zhan, Douglas R Spitz, Michael K Schultz, Apollina Goel
Therapeutic advances have markedly prolonged overall survival in multiple myeloma (MM) but the disease currently remains incurable. In a panel of MM cell lines (MM.1S, OPM-2, H929, and U266), using CD138 immunophenotyping, side population staining, and stem cell-related gene expression, we demonstrate the presence of stem-like tumor cells. Hypoxic culture conditions further increased CD138low stem-like cells with upregulated expression of OCT4 and NANOG. Compared to MM cells, these stem-like cells maintained lower steady-state pro-oxidant levels with increased uptake of the fluorescent deoxyglucose analog...
2016: PloS One
https://www.readbyqxmd.com/read/27902730/spectrum-of-cerebrovascular-disease-in-patients-with-multiple-myeloma-undergoing-chemotherapy-results-of-a-case-control-study
#18
Archana Hinduja, Kaustubh Limaye, Rahul Ravilla, Appalnaidu Sasapu, Xenofon Papanikolaou, Lai Wei, Michel Torbey, Sarah Waheed
OBJECTIVES: Patients with multiple myeloma (MM) are at increased risk of arterial thrombosis. Our aim was to determine the risk factors, mechanisms and outcome of strokes in these patients. METHODS: We conducted a retrospective matched case-control study from our database of MM patients enrolled in Total Therapy (TT) 2, TT3a and TT3b protocols who developed a vascular event (transient ischemic attack, ischemic stroke, or intracerebral hemorrhage) from October 1998 to January 2014...
2016: PloS One
https://www.readbyqxmd.com/read/27900520/nuclear-medicine-imaging-of-multiple-myeloma-particularly-in-the-relapsed-setting
#19
REVIEW
Esther G M de Waal, Andor W J M Glaudemans, Carolien P Schröder, Edo Vellenga, Riemer H J A Slart
Multiple myeloma (MM) is characterized by a monoclonal plasma cell population in the bone marrow. Lytic lesions occur in up to 90 % of patients. For many years, whole-body X-ray (WBX) was the method of choice for detecting skeleton abnormalities. However, the value of WBX in relapsing disease is limited because lesions persist post-treatment, which restricts the capacity to distinguish between old, inactive skeletal lesions and new, active ones. Therefore, alternative techniques are necessary to visualize disease activity...
November 29, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27900079/solitary-pleural-myeloma-diagnosed-by-semi-rigid-thoracoscopy-a-case-report-and-literature-review
#20
Jin-Sheng Ouyang, Yu-Ping Li, Peng Li, Min Ye, Jun-Ru Ye, Bei-Bei Wang, Ying Zhou, Cheng-Shui Chen
Multiple myeloma (MM) is characterized by abnormal proliferation of neoplastic plasma cells. Pleural effusion as an initial presentation of this disease is rare, as is true pleural myeloma. We herein present a case of solitary pleural myelomatous lesion in a 70-year-old male patient diagnosed by pleural biopsy via semi-rigid thoracoscopy followed by histopathological examination. Furthermore, a review of the related English literature identified 22 cases of pleural myeloma, only 3 of which were diagnosed by video-assisted thoracoscopy...
November 2016: Molecular and Clinical Oncology
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