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Lenalidomide

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https://www.readbyqxmd.com/read/28645562/anti-myeloma-effects-of-ruxolitinib-combined-with-bortezomib-and-lenalidomide-a-rationale-for-jak-stat-pathway-inhibition-in-myeloma-patients
#1
Mariana B de Oliveira, Veruska L Fook-Alves, Angela I P Eugenio, Rodrigo C Fernando, Luiz Felipe G Sanson, Mariana F de Carvalho, Walter M T Braga, Faith E Davies, Gisele W B Colleoni
JAK proteins have been linked with survival and proliferation of multiple myeloma (MM) cells; therefore, JAK inhibition could be a therapeutic strategy for MM. We evaluated JAK1 and JAK2 expression in MM patients and the effects of JAK/STAT pathway inhibition on apoptosis, cell cycle, gene and protein expression in RPMI-8226 and U266 MM cell lines. 57% of patients presented overexpression of JAK2 and 27%, of JAK1. After treatment with ruxolitinib and bortezomib, RPMI-8226 and U266 presented 50% of cells in late apoptosis, reduction of anti-apoptotic genes expression and higher number of cells in SubG0 phase...
June 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28645118/outcome-of-patients-treated-for-myelodysplastic-syndromes-with-5q-deletion-after-failure-of-lenalidomide-therapy
#2
Thomas Prebet, Thomas Cluzeau, Sophie Park, Mikkael A Sekeres, Ulrich Germing, Lionel Ades, Uwe Platzbecker, Katharina Gotze, Norbert Vey, Esther Oliva, Mary M Sugrue, Cecile Bally, Charikleia Kelaidi, Najla Al Ali, Pierre Fenaux, Steven D Gore, Rami Komrokji
While lenalidomide (LEN) is the standard of care for the lower-risk myelodysplastic syndromes (MDS) patients with deletion 5q, 35% will not respond to or do not tolerate the drug. Moreover, most of the patients will lose their response after a few years. Defining the outcome of patients with LEN failure and determining the impact of subsequent therapies is therefore important to develop alternative strategies. Based on an international collaboration, we were able to compile a total of 392 patient cases of lower-risk MDS patients with 5q deletion and to analyze their outcome after failure of lenalidomide...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643330/muc1-c-is-a-target-in-lenalidomide-resistant-multiple-myeloma
#3
Li Yin, Ashujit Tagde, Reddy Gali, Yu-Tzu Tai, Teru Hideshima, Kenneth Anderson, David Avigan, Donald Kufe
Lenalidomide (LEN) acts directly on multiple myeloma (MM) cells by inducing cereblon-mediated degradation of interferon regulatory factor 4, Ikaros (IKZF)1 and IKZF3, transcription factors that are essential for MM cell survival. The mucin 1 (MUC1) C-terminal transmembrane subunit (MUC1-C) oncoprotein is aberrantly expressed by MM cells and protects against reactive oxygen species (ROS)-mediated MM cell death. The present studies demonstrate that targeting MUC1-C with GO-203, a cell-penetrating peptide inhibitor of MUC1-C homodimerization, is more than additive with LEN in downregulating the WNT/β-catenin pathway, suppressing MYC, and inducing late apoptosis/necrosis...
June 23, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28642620/pomalidomide-bortezomib-and-low-dose-dexamethasone-in-lenalidomide-refractory-and-proteasome-inhibitor-exposed-myeloma
#4
P G Richardson, C C Hofmeister, N S Raje, D S Siegel, S Lonial, J Laubach, Y A Efebera, D H Vesole, A K Nooka, J Rosenblatt, D Doss, M H Zaki, A Bensmaine, J Herring, Y Li, L Watkins, M S Chen, K C Anderson
This phase 1 dose-escalation study evaluated pomalidomide, bortezomib (subcutaneous (SC) or intravenous (IV)) and low-dose dexamethasone (LoDEX) in lenalidomide-refractory and proteasome inhibitor-exposed relapsed or relapsed and refractory multiple myeloma (RRMM). In 21-day cycles, patients received pomalidomide (1-4 mg days 1-14), bortezomib (1-1.3 mg/m(2) days 1, 4, 8 and 11 for cycles 1-8; days 1 and 8 for cycle ⩾9) and LoDEX. Primary endpoint was to determine the maximum tolerated dose (MTD). Thirty-four patients enrolled: 12 during escalation, 10 in the MTD IV bortezomib cohort and 12 in the MTD SC bortezomib cohort...
June 2, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28642303/molecular-analysis-of-myelodysplastic-syndrome-with-isolated-del-5q-reveals-a-specific-spectrum-of-molecular-mutations-with-prognostic-impact-a-study-on-123-patients-and-27-genes
#5
Manja Meggendorfer, Claudia Haferlach, Wolfgang Kern, Torsten Haferlach
The only cytogenetic aberration defining a myelodysplastic syndrome subtype is the deletion of the long arm of chromosome 5, giving with morphological features the diagnosis of myelodysplastic syndrome with isolated del(5q). These patients show a good prognosis and respond to treatment such as lenalidomide, but some cases progress to acute myeloid leukemia. However, the molecular mutation pattern is rarely characterized. Therefore, we investigated a large cohort of 123 myelodysplastic syndrome patients with isolated del(5q) diagnosed following the World Health Organization classifications 2008 and 2016 by sequencing 27 genes...
June 22, 2017: Haematologica
https://www.readbyqxmd.com/read/28641472/long-term-health-related-quality-of-life-in-transplant-ineligible-patients-with-newly-diagnosed-multiple-myeloma-receiving-lenalidomide-and-dexamethasone
#6
Dan T Vogl, Michel Delforge, Kevin Song, Shien Guo, Craig J Gibson, Annette Ervin-Haynes, Thierry Facon
The FIRST trial demonstrated that continuous therapy with lenalidomide and dexamethasone (Rd) prolongs overall survival (OS) and improves health-related quality of life (HRQoL) during the first 18 months of therapy in newly diagnosed multiple myeloma (NDMM) patients. However, patient-reported HRQoL data were not collected after 18 months. We therefore estimated HRQoL scores based on time-varying data collected during progression-free follow-up after 18 months. During the initial 18 months of Rd, observed changes from baseline were within the 95% confidence interval of the predictive models at 33 of 35 time points across 7 HRQoL scores...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28639485/increased-shisa3-expression-characterizes-chronic-lymphocytic-leukemia-patients-sensitive-to-lenalidomide
#7
Rossana Maffei, Stefania Fiorcari, Silvia Martinelli, Stefania Benatti, Jenny Bulgarelli, Lara Rizzotto, Giulia Debbia, Rita Santachiara, Gian Matteo Rigolin, Francesco Forconi, Davide Rossi, Luca Laurenti, Giuseppe A Palumbo, Daniele Vallisa, Antonio Cuneo, Gianluca Gaidano, Mario Luppi, Roberto Marasca
Lenalidomide is a therapeutically effective drug in chronic lymphocytic leukemia (CLL). Twenty-seven CLL patients were treated with lenalidomide in a phase II clinical trial. Ten patients were grouped as responders (R) and 6 as nonresponders (NR). We evaluated T lymphocytes, NK, monocytes and dendritic cells at baseline and after treatment. A gene expression analysis was performed on 16 CLL samples collected before treatment. The levels of immune cells or immune-related cytokines are not different between R and NR patients...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28637843/poems-syndrome-a-rare-cause-of-exudative-ascites-and-chronic-peripheral-neuropathy
#8
Omar Al-Mayoof, Hana Al Sughaiyer, Wuroud Abuomar, Maria Khan
POEMS syndrome (Peripheral neuropathy, Organomegaly, Endocrinopathy, M protein, Skin changes) is a rare plasma cell disorder with multisystem involvementA 40-year-old man with a chronic history of unexplained peripheral neuropathy , presented with exudative ascites.He was found to have an incidental osteolytic lesion of the sacrum proven to be a plasmacytoma. Immunoelectrophoresis for monoclonal protein was negative.In addition, the patient was found to have hepatosplenomegaly, erectile dysfunction, hyperprolactinaemia and hypothyroidism...
June 20, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28632471/lenalidomide-as-a-treatment-for-relapsed-al-amyloidosis-in-an-hiv-positive-patient
#9
Johanna Denman, Kaveh Manavi, Mark Cook
We present a case of an HIV-positive man with systemic immunoglobulin light chain (AL) amyloid with cardiac involvement. At relapse, he was treated with lenalidomide and dexamethasone having previously developed autonomic neuropathy with bortezomib-based chemotherapy. The patient achieved a serological complete response with symptomatic improvement. After 11 cycles, lenalidomide was discontinued due to extensive ischaemia of the gastrointestinal tract. The patient remains symptomatically stable with normal levels of serum-free light chains 11 months after the treatment was discontinued...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28630385/low-dose-of-lenalidomide-enhances-nk-cell-activity-possible-implication-as-an-adjuvant
#10
Kiandokht Borhani, Taravat Bamdad, Tayebeh Hashempour
BACKGROUND: Lenalidomide, a synthetic immunomodulatory drug, has a wide range of features including anti-angiogenic and anti-proliferative properties. To date, researchers have shown that lenalidomide is capable of ameliorating the immune system factors and antitumor responses. Most researchers have reported that lenalidomide enhances the immune response in certain cancer patients through several pathways including the stimulation of Natural Killer cells; notwithstanding, it is still crucial to investigate the effect of lenalidomide on the activity of NK cell cytotoxicity both in vitro and in vivo...
June 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28628013/modulation-of-antitumor-immune-response-in-mouse-prostate-cancer-model
#11
N Mitskevich, T Tsertsvadze, K Mchedlishvili, K Matchavariani, G Guruli
Aim of study - prostate cancer is second most common cancer in men worldwide, and fifth leading cause of death from cancer in men (6.6% of the total men deaths). Unfortunately, once cancer spreads outside of prostate, it becomes incurable. Androgen deprivation can provide some relief, but resistance will develop eventually, and at that time no effective treatment options are left to the patient. Therefore, the search of alternative treatment modalities is paramount. In this article we evaluated the role of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator - Lenalidomide and their possible impact on the immune response in the murine prostate cancer model...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28622959/a-phase-i-ii-trial-of-panobinostat-in-combination-with-lenalidomide-in-patients-with-relapsed-or-refractory-hodgkin-lymphoma
#12
Joseph J Maly, Beth A Christian, Xiaohua Zhu, Lai Wei, Jennifer L Sexton, Samantha M Jaglowski, Steven M Devine, Todd A Fehniger, Nina D Wagner-Johnston, Mitch A Phelps, Nancy L Bartlett, Kristie A Blum
BACKGROUND: Lenalidomide and panobinostat have shown single-agent efficacy of 14% to 50% and 27% to 58%, respectively, in Hodgkin lymphoma (HL). This phase I/II study was conducted to determine the maximum tolerated dose (MTD), safety, and efficacy of lenalidomide combined with panobinostat in relapsed/refractory HL. PATIENTS AND METHODS: In the phase I trial, previously treated patients with classical or lymphocyte-predominant HL received escalating doses of lenalidomide on days 1 to 21 and panobinostat 3 times a week (TIW) every 28 days...
June 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28622306/changes-in-uninvolved-immunoglobulins-during-induction-therapy-for-newly-diagnosed-multiple-myeloma
#13
P Ravi, S Kumar, W Gonsalves, F Buadi, M Q Lacy, R S Go, A Dispenzieri, P Kapoor, J A Lust, D Dingli, Y Lin, S J Russell, N Leung, M A Gertz, R A Kyle, P L Bergsagel, S V Rajkumar
Little is known about the impact of multiple myeloma (MM) treatment on uninvolved immunoglobulins (Ig). We identified 448 patients who received high-dose dexamethasone (HD-DEX), lenalidomide and dexamethasone (RD), bortezomib and dexamethasone (VD), bortezomib, cyclophosphamide and dexamethasone (VCD) or bortezomib, lenalidomide and dexamethasone (VRD) for newly diagnosed MM at our institution between 2000 and 2013, and who had available data on absolute lymphocyte count (ALC) and quantitative uninvolved Ig at baseline and at the end of four cycles of therapy...
June 16, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28620163/natural-history-of-relapsed-myeloma-refractory-to-immunomodulatory-drugs-and-proteasome-inhibitors-a-multicenter-imwg-study
#14
S K Kumar, M A Dimopoulos, E Kastritis, E Terpos, H Nahi, H Goldschmidt, J Hillengass, X Leleu, M Beksac, M Alsina, A Oriol, M Cavo, E M Ocio, M V Mateos, E K O'Donnell, R Vij, H M Lokhorst, N W C J van de Donk, C Min, T Mark, I Turesson, M Hansson, H Ludwig, S Jagannath, M Delforge, C Kyriakou, P Hari, U Mellqvist, S Z Usmani, D Dytfeld, A Z Badros, P Moreau, K Kim, P R Otero, J H Lee, C Shustik, D Waller, W J Chng, S Ozaki, J-J Lee, J de la Rubia, H S Eom, L Rosinol, J J Lahuerta, A Sureda, J S Kim, B G M Durie
Introduction of new myeloma therapies offers new options for patients refractory to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). In this multicenter study, patients with relapsed multiple myeloma, who have received at least three prior lines of therapy, are refractory to both an IMiD (lenalidomide or pomalidomide) and a PI (bortezomib or carfilzomib), and have been exposed to an alkylating agent were identified. The time patients met the above criteria was defined as time zero (T0). Five hundred and forty-three patients diagnosed between 2006 and 2014 were enrolled in this study...
May 12, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28619709/loss-of-fam46c-promotes-cell-survival-in-myeloma
#15
Yuan Xiao Zhu, Chang-Xin Shi, Laura A Bruins, Patrick Jedlowski, Xuewei Wang, K Martin Kortüm, Moulun Luo, Jonathan Ahmann, Esteban Braggio, A Keith Stewart
FAM46C is one of the most recurrently mutated genes in multiple myeloma (MM), however its role in disease pathogenesis has not been determined. Here we demonstrate that wild type (WT) FAM46C overexpression induces substantial cytotoxicity in MM cells. In contrast, FAM46C mutations found in MM patients abrogate this cytotoxicity, indicating a survival advantage conferred by the FAM46C mutant phenotype. WT FAM46C overexpression downregulated IRF4, CEBPB, and MYC and upregulated immunoglobulin (Ig) light chain and HSPA5/BIP Furthermore, pathway analysis suggests that enforced FAM46C expression activated the unfolded protein response (UPR) pathway and induced mitochondrial dysfunction...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28601492/new-agents-in-multiple-myeloma-an%C3%A2-examination-of-safety-profiles
#16
REVIEW
Sara Bringhen, Edwin De Wit, Meletios-Athanassios Dimopoulos
Numerous treatments are available for relapsed and/or refractory multiple myeloma (MM), with safety profiles varying across drug classes and across agents within the same class. Thus, it is important to understand the toxicities of each antimyeloma agent when making treatment decisions. Neutropenia is commonly associated with lenalidomide and pomalidomide, and may be common with histone deacetylase (HDAC) inhibitors, but is relatively unusual with thalidomide, bortezomib, and carfilzomib. Infection was common in trials of lenalidomide and pomalidomide, and upper respiratory tract infection and pneumonia have been seen with carfilzomib...
May 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28600436/accurate-quantification-of-chromosomal-lesions-via-short-tandem-repeat-analysis-using-minimal-amounts-of-dna
#17
Johann-Christoph Jann, Daniel Nowak, Florian Nolte, Stephanie Fey, Verena Nowak, Julia Obländer, Jovita Pressler, Iris Palme, Christina Xanthopoulos, Alice Fabarius, Uwe Platzbecker, Aristoteles Giagounidis, Katharina Götze, Anne Letsch, Detlef Haase, Richard Schlenk, Gesine Bug, Michael Lübbert, Arnold Ganser, Ulrich Germing, Claudia Haferlach, Wolf-Karsten Hofmann, Maximilian Mossner
BACKGROUND: Cytogenetic aberrations such as deletion of chromosome 5q (del(5q)) represent key elements in routine clinical diagnostics of haematological malignancies. Currently established methods such as metaphase cytogenetics, FISH or array-based approaches have limitations due to their dependency on viable cells, high costs or semi-quantitative nature. Importantly, they cannot be used on low abundance DNA. We therefore aimed to establish a robust and quantitative technique that overcomes these shortcomings...
June 9, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28598585/epithelioid-hemangioendotheliomas-of-the-liver-and-lung-in-children-and-adolescents
#18
REVIEW
Simone Hettmer, Geoffroy Andrieux, Jochen Hochrein, Philipp Kurz, Jochen Rössler, Silke Lassmann, Martin Werner, Nikolas von Bubnoff, Christoph Peters, Ewa Koscielniak, Monika Sparber-Sauer, Charlotte Niemeyer, Thomas Mentzel, Hauke Busch, Melanie Boerries
Epithelioid hemangioendothelioma (EHE) is a rare, vascular sarcoma. Visceral forms arise in the liver/ lungs. We review the clinical and molecular phenotype of pediatric visceral EHE based on the case of a 9-year-old male child with EHE of the liver/lungs. His tumor expressed the EHE-specific fusion oncogene WWTR1-CAMTA1. Molecular characterization revealed a low somatic mutation rate and activated interferon signaling, angiogenesis regulation, and blood vessel remodeling. After polychemotherapy and resection of lung tumors, residual disease remained stable on oral lenalidomide...
June 9, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28596474/lenalidomide-increases-human-dendritic-cell-maturation-in-multiple-myeloma-patients-targeting-monocyte-differentiation-and-modulating-mesenchymal-stromal-cell-inhibitory-properties
#19
Federica Costa, Rosanna Vescovini, Marina Bolzoni, Valentina Marchica, Paola Storti, Denise Toscani, Fabrizio Accardi, Laura Notarfranchi, Benedetta Dalla Palma, Cristina Manferdini, Sabrina Manni, Giannalisa Todaro, Gina Lisignoli, Francesco Piazza, Franco Aversa, Nicola Giuliani
The use of Lenalidomide (LEN), to reverse tumor-mediated immune suppression and amplify multiple myeloma-specific immunity is currently being explored. Particularly, LEN effects on dendritic cells (DCs) are still unclear. In this study, we investigated the potential effect of LEN on DC differentiation and activity. DCs were differentiated either from CD14+ cells obtained from patients with multiple myeloma or from a human monocytic cell line.LEN, at the concentration range reached in vivo, significantly increased the median intensity expression of HLA-DR, CD86 and CD209 by DCs derived from both bone marrow and peripheral myeloma monocytes and enhanced the production of Interleukin-8, C-C motif chemokine ligand (CCL) 2, CCL5 and tumor necrosis factor-α...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28592763/malignant-lymphoma-pathophysiology-and-current-therapy
#20
Koji Izutsu
Recent advances in the understanding of molecular pathogenesis of lymphoma have enabled us to clearly define disease entity by means of a disease-specific gene mutation and to select candidates for novel targeted therapy. In this review three different clinically relevant topics related to the molecular pathogenesis of lymphoma were covered. In the 2016 revision of the World Health Organization classification of lymphoid malignancies, firstly, disease-specific mutations such as MYD88 L265P in Waldenström macroglobulinemia and BRAF V600E in hairy cell leukemia were incorporated into diagnostic tests, and secondly, the determination of cell-of-origin in diffuse large B-cell lymphoma (DLBCL) was strongly recommended in diagnosis...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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