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Treatment of myeloma

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https://www.readbyqxmd.com/read/29784907/a-predictive-model-for-risk-of-early-grade-%C3%A2-3-infection-in-patients-with-multiple-myeloma-not-eligible-for-transplant-analysis-of-the-first-trial
#1
Charles Dumontet, Cyrille Hulin, Meletios A Dimopoulos, Andrew Belch, Angela Dispenzieri, Heinz Ludwig, Philippe Rodon, Jan Van Droogenbroeck, Lugui Qiu, Michele Cavo, Ann Van de Velde, Juan José Lahuerta, Olivier Allangba, Jae Hoon Lee, Eileen Boyle, Aurore Perrot, Philippe Moreau, Salomon Manier, Michel Attal, Murielle Roussel, Mohamad Mohty, Jean Yves Mary, Alexandre Civet, Bruno Costa, Antoine Tinel, Yann Gaston-Mathé, Thierry Facon
Infections are a major cause of death in patients with multiple myeloma. A post hoc analysis of the phase 3 FIRST trial was conducted to characterize treatment-emergent (TE) infections and study risk factors for TE grade ≥ 3 infection. The number of TE infections/month was highest during the first 4 months of treatment (defined as early infection). Of 1613 treated patients, 340 (21.1%) experienced TE grade ≥ 3 infections in the first 18 months and 56.2% of these patients experienced their first grade ≥ 3 infection in the first 4 months...
April 26, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29784741/management-of-multiple-myeloma
#2
Shaji K Kumar
The most recent NCCN Guidelines for Multiple Myeloma include a ranking of the many treatment options for various settings as "preferred," "other," and "useful in certain circumstances." For patients eligible for autologous stem cell transplant (ASCT), the preferred regimen remains bortezomib/lenalidomide/dexamethasone (category 1) or bortezomib/cyclophosphamide/dexamethasone. Upfront ASCT also remains a preferred strategy for patients who are transplant-eligible, despite highly effective newer agents such as induction therapy...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784015/induction-of-multiple-myeloma-cancer-stem-cell-apoptosis-using-conjugated-anti-abcg2-antibody-with-epirubicin-loaded-microbubbles
#3
Fangfang Shi, Miao Li, Jing Wang, Di Wu, Meng Pan, Mei Guo, Jun Dou
BACKGROUND: Multiple myeloma (MM) currently remains largely incurable. Cancer stem cells (CSCs) are believed to be responsible for drug resistance and eventual relapse. In this study, we exploited a novel agent to evaluate its inhibitory effect on MM CSCs. METHODS: Epirubicin (EPI)-loaded lipid microbubbles (MBs) conjugated with anti-ABCG2 monoclonal antibody (EPI-MBs + mAb) were developed and their effect on MM 138- CD34- CSCs isolated from human MM RPMI 8226 cell line plus ultrasound exposure in vitro and in vivo in a nonobese diabetic/severe combined immunodeficient mouse model were assessed...
May 21, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29783691/old-and-young-actors-playing-novel-roles-in-the-drama-of-multiple-myeloma-bone-marrow-microenvironment-dependent-drug-resistance
#4
REVIEW
Sabrina Manni, Marilena Carrino, Gianpietro Semenzato, Francesco Piazza
Multiple myeloma (MM) is the second most frequent hematologic cancer. In addition to the deleterious effects of neoplastic plasma cell growth and spreading during the disease evolution, this tumor is characterized by the serious pathological consequences due to the massive secretion of monoclonal immunoglobulins and by the derangement of bone physiology with progressive weakening of the skeleton. Despite significant progresses having been made in the last two decades in the therapeutic management of this plasma cell tumor, MM remains invariably lethal, due to its extremely complex genetic architecture and to the constant protection it receives from the tumor niche, which is represented by the bone marrow microenvironment...
May 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29781462/multiple-myeloma-detecting-genetic-changes-through-bone-marrow-biopsy-and-the-influence-on-care
#5
Donna Catamero
Knowledge of genetic mutations and how these affect patient outcomes is rapidly expanding in the care of individuals diagnosed with multiple myeloma (MM). Genetic analysis of bone marrow biopsies now provides information about diagnosis,response to treatment, and prognosis. Oncology nurses need to understand the science and meaning of bone marrow biopsy reports, including the implications of genetic alterations and minimal residual disease. This will allow them to provide care, support, and education related to MM and its treatment to patients and their families...
June 1, 2018: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/29780393/immunomodulatory-drugs-exert-anti-leukemia-effects-in-acute-myeloid-leukemia-by-direct-and-immunostimulatory-activities
#6
Aude Le Roy, Thomas Prébet, Rémy Castellano, Armelle Goubard, Florence Riccardi, Cyril Fauriat, Samuel Granjeaud, Audrey Benyamine, Céline Castanier, Florence Orlanducci, Amira Ben Amara, Frédéric Pont, Jean-Jacques Fournié, Yves Collette, Jean-Louis Mege, Norbert Vey, Daniel Olive
Immunomodulatory drugs (IMiDs) are anticancer drugs with immunomodulatory, anti-angiogenesis, anti-proliferative, and pro-apoptotic properties. IMiDs are currently used for the treatment of multiple myeloma, myelodysplastic syndrome, and B-cell lymphoma; however, little is known about efficacy in acute myeloid leukemia (AML). We proposed in this study to investigate the relevance of IMiDs therapy for AML treatment. We evaluated the effect of IMiDs on primary AML blasts ( n  = 24), and the impact in natural killer (NK) cell-mediated immunosurveillance of AML...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29779352/-effect-of-1q21-amplification-on-bortezomib-therapeutic-response-and-prognosis-of-newly-diagnosed-multiple-myeloma-patients
#7
X L Liu, P Y Yang, X Y Yu, J C Chen, X L Liu, J Bai, Y M Liu, H He, J N Sun, H Q Fan, C Zhang, Y Zhang, K J Su, C S Liu, Y H Tan, S J Gao, W Li, F Y Jin
Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51...
May 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29779211/cutaneous-sarcoidosis-a-new-subset-in-the-spectrum-of-paraneoplastic-dermatoses
#8
M El-Khalawany, A Mosbeh, S Aboeldahab, S Ali
BACKGROUND: Sarcoidosis is a well-described disease that can be associated with various malignancies; however, this correlation is still not fully clarified. AIM: To determine the clinical and histological features, demographic characteristics, and prognosis of patients diagnosed with paraneoplastic sarcoidosis (PS). METHODS: This observational cohort prospective study included all patients diagnosed as cutaneous sarcoidosis. All patients were monitored for therapeutic response, prognosis, and any associated diseases or malignancies...
May 20, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29778492/tanovea%C3%A2-for-the-treatment-of-lymphoma-in-dogs
#9
REVIEW
Erik De Clercq
Tanovea® (first named GS-9219, then VDC-1101, generic name: rabacfosadine) is a pro-prodrug or "double" prodrug of PMEG [9-(2-phosphonylmethoxyethyl)guanine], which has been conditionally approved by the US FDA (Food and Drug Administration) for the treatment of lymphoma in dogs. Tanovea has been demonstrated to be effective against non-Hodgkin's lymphoma (NHL) in dogs, as well as canine cutaneous T-cell lymphoma, spontaneous canine multiple myeloma, naïve canine multicentric lymphoma and relapsed canine B-cell lymphoma...
May 17, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29776984/impact-of-psychiatric-comorbidities-on-health-care-utilization-and-cost-of-care-in-multiple-myeloma
#10
Shehzad Niazi, Ryan D Frank, Mayank Sharma, Vivek Roy, Steve Ames, Teresa Rummans, Aaron Spaulding, Taimur Sher, Meghna Ailawadhi, Kirtipal Bhatia, Salman Ahmed, Winston Tan, Asher Chanan-Khan, Sikander Ailawadhi
Approximately one third of cancer patients suffer from comorbid mood disorders that are associated with increased cost and poorer outcomes. The majority of patients with multiple myeloma (MM) are treated with corticosteroids; as many as three fourths of those taking corticosteroids develop neuropsychiatric complications, likely increasing morbidity and cost of care. MM patients diagnosed between 1991 and 2010 and reported in the Surveillance Epidemiology, and End Results-Medicare database were characterized as MM-Only, MM+Psychiatric (any psychiatric condition, preexisting or post-MM), or MM+Depression (depression as the only psychiatric diagnosis, preexisting or post-MM)...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29774521/patient-reported-outcomes-of-multiple-myeloma-patients-treated-with-panobinostat-after-%C3%A2-2-lines-of-therapy-based-on-the-international-phase-3-randomized-double-blind-placebo-controlled-panorama-1-trial
#11
Paul G Richardson, Robert L Schlossman, Anuja N Roy, Ashok Panneerselvam, Suddhasatta Acharyya, Monika Sopala, Sagar Lonial
The phase 3 PANORAMA-1 trial led to regulatory approvals of panobinostat (PAN) in combination with bortezomib (BTZ) and dexamethasone (DEX) for the treatment of multiple myeloma after ≥2 prior regimens, including BTZ and an immunomodulatory drug. Patient-reported outcomes (PROs) were assessed in PANORAMA-1, with data available for 73 patients in the PAN + BTZ + DEX arm and 74 patients in the placebo (PBO) + BTZ + DEX arm. Per the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), global health status/quality of life (QoL) scores initially declined with PAN + BTZ + DEX during the first 24 weeks before approaching baseline scores and remaining steady during the next 24 weeks, with no difference between arms at Week 48...
May 17, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29774113/ezh2-inhibitors-sensitize-myeloma-cell-lines-to-panobinostat-resulting-in-unique-combinatorial-transcriptomic-changes
#12
Taylor Harding, Jessica Swanson, Brian Van Ness
Multiple myeloma (MM) remains a largely incurable hematologic cancer due to an inability to broadly target inevitable drug-resistant relapse. Epigenetic abnormalities are abundantly present in multiple myeloma and have increasingly demonstrated critical roles for tumor development and relapse to standard therapies. Accumulating evidence suggests that the histone methyltransferase EZH2 is aberrantly active in MM. We tested the efficacy of EZH2 specific inhibitors in a large panel of human MM cell lines (HMCLs) and found that only a subset of HMCLs demonstrate single agent sensitivity despite ubiquitous global H3K27 demethylation...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773987/celastrol-attenuates-the-invasion-and-migration-and-augments-the-anticancer-effects-of-bortezomib-in-a-xenograft-mouse-model-of-multiple-myeloma
#13
Muthu K Shanmugam, Kwang S Ahn, Jong H Lee, Radhamani Kannaiyan, Nurulhuda Mustafa, Kanjoormana A Manu, Kodappully S Siveen, Gautam Sethi, Wee J Chng, Alan P Kumar
Several lines of evidence have demonstrated that deregulated activation of NF-κB plays a pivotal role in the initiation and progression of a variety of cancers including multiple myeloma (MM). Therefore, novel molecules that can effectively suppress deregulated NF-κB upregulation can potentially reduce MM growth. In this study, the effect of celastrol (CSL) on patient derived CD138+ MM cell proliferation, apoptosis, cell invasion, and migration was investigated. In addition, we studied whether CSL can potentiate the apoptotic effect of bortezomib, a proteasome inhibitor in MM cells and in a xenograft mouse model...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29773595/therapeutic-effects-of-the-novel-subtype-selective-histone-deacetylase-hdac-inhibitor-chidamide-on-myeloma-associated-bone-disease
#14
Jingsong He, Qingxiao Chen, Huiyao Gu, Jing Chen, Enfan Zhang, Xing Guo, Xi Huang, Haimeng Yan, DongHua He, Yang Yang, Yi Zhao, Gang Wang, Huang He, Qing Yi, Zhen Cai
Histone deacetylases are promising therapeutic targets in hematological malignancies. In the present work, we investigated the effect of chidamide, a new subtype-selective histone deacetylase inhibitor that was independently produced in China, on multiple myeloma and its associated bone diseases using different models. The cytotoxicity of chidamide toward myeloma is due to its induction of cell apoptosis and cell cycle arrest by increasing the levels of caspase family proteins, including p21 and p27, among others...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773319/advancements-in-nanomedicine-for-multiple-myeloma
#15
REVIEW
Alexandre Detappe, Mark Bustoros, Tarek H Mouhieddine, P Peter Ghoroghchian
In the past decades, considerable progress has been made in our understanding and treatment of multiple myeloma. Several challenges remain including our abilities to longitudinally image tumor responses to treatment, to combine various therapeutic agents with different mechanisms of action but with overlapping toxicities, and to efficiently harness the power of the immune system to augment remission and/or to induce permanent cures. Nanomedicine may help to address many of these outstanding issues, affording novel diagnostic capabilities and offering disruptive technologies that promise to revolutionize treatment...
May 14, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29768064/a-look-at-treatment-strategies-for-relapsed-multiple-myeloma
#16
Giusy Cetani, Mario Boccadoro, Stefania Oliva
Multiple myeloma treatment considerably improved during the past decade, thanks to novel effective drugs, a better understanding of myeloma biology and clonal heterogeneity, and an improved management of toxicities. The choice of regimen at relapse is usually based on prior response, toxicities, age and comorbidities of relapsed patients. Areas covered: A review was performed of the most recent and effective therapeutic strategies for the relapsed myeloma setting, by documenting the latest clinical evidence from phase II and III clinical trials...
May 16, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29766549/leukocytoclastic-vasculitis-associated-with-immunoglobulin-a-lambda-monoclonal-gammopathy-of-undetermined-significance-a-case-report-and-review-of-previously-reported-cases
#17
Hiroshi Umemura, Osamu Yamasaki, Keiji Iwatsuki
Leukocytoclastic vasculitis is often associated with immunoglobulin (Ig)A deposition on the vascular walls. IgA-associated leukocytoclastic vasculitis comprises various underlying diseases. Hematological disorders that can be minor triggers include multiple myeloma and monoclonal gammopathy of undetermined significance. Here, we present the case of a 78-year-old woman with leukocytoclastic vasculitis associated with monoclonal gammopathy of undetermined significance of the IgA lambda chain. Oral steroid administration initially showed remission of vasculitis; however, the condition recurred after four attempts of treatment withdrawal...
May 15, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29765356/soluble-and-cell-cell-mediated-drivers-of-proteasome-inhibitor-resistance-in-multiple-myeloma
#18
REVIEW
Mariah L Farrell, Michaela R Reagan
It is becoming clear that myeloma cell-induced disruption of the highly organized bone marrow components (both cellular and extracellular) results in destruction of the marrow and support for multiple myeloma (MM) cell proliferation, survival, migration, and drug resistance. Since the first phase I clinical trial on bortezomib was published 15 years ago, proteasome inhibitors (PIs) have become increasingly common for treatment of MM and are currently an essential part of any anti-myeloma combination therapy...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29761903/the-combination-of-a-sphingosine-kinase-2-inhibitor-abc294640-and-a-bcl-2-inhibitor-abt-199-displays-synergistic-anti-myeloma-effects-in-myeloma-cells-without-a-t-11-14-translocation
#19
Pasupathi Sundaramoorthy, Cristina Gasparetto, Yubin Kang
Multiple myeloma (MM) remains an incurable disease in need of the development of novel therapeutic agents and drug combinations. ABT-199 is a specific Bcl-2 inhibitor in clinical trials for MM; however, its activity as a single agent was limited to myeloma patients with the t(11;14) translocation who acquire resistance due to co-expression of Mcl-1 and Bcl-xL. These limitations preclude its use in a broader patient population. We have recently found that a sphingosine kinase 2-specific inhibitor (ABC294640) induces apoptosis in primary human CD138+ cells and MM cell lines...
May 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29759561/going-the-distance-are-we-losing-patients-along-the-multiple-myeloma-treatment-pathway
#20
REVIEW
Evangelos Terpos, Florence Suzan, Hartmut Goldschmidt
Despite data suggesting that individuals with multiple myeloma can benefit from receiving several lines of therapy, and guidelines recommending treatment after relapse, a recent European patient chart review found that only 61% of patients receive second-line treatment. The review found that factors such as old age and previous adverse events lead to physicians deciding not to treat after relapse. However, given the large number of regimens available, treatment can be tailored to individual patients' needs and supportive care measures can help with the management of adverse effects...
June 2018: Critical Reviews in Oncology/hematology
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