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Lenalidomide

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https://www.readbyqxmd.com/read/28314699/safety-and-tolerability-of-idelalisib-lenalidomide-and-rituximab-in-relapsed-and-refractory-lymphoma-the-alliance-for-clinical-trials-in-oncology-a051201-and-a051202-phase-1-trials
#1
Sonali M Smith, Brandelyn N Pitcher, Sin-Ho Jung, Nancy L Bartlett, Nina Wagner-Johnston, Steven I Park, Kristy L Richards, Amanda F Cashen, Anthony Jaslowski, Scott E Smith, Bruce D Cheson, Eric Hsi, John P Leonard
BACKGROUND: A new generation of biological and targeted agents might potentially replace traditional cytotoxic agents in lymphoma. Lenalidomide plus rituximab was felt to be a safe and promising backbone based on available data. Idelalisib is an oral phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor that has promising activity as a monotherapy in refractory indolent lymphomas. The primary objective of these two trials was to determine the maximum tolerated dose of lenalidomide in combination with rituximab and idelalisib in relapsed follicular and mantle cell lymphoma...
March 14, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28304402/prospective-longitudinal-study-on-quality-of-life-in-relapsed-refractory-multiple-myeloma-patients-receiving-second-or-third-line-lenalidomide-or-bortezomib-treatment
#2
X Leleu, C Kyriakou, I Vande Broek, P Murphy, P Bacon, P Lewis, H Gilet, B Arnould, M T Petrucci
Treatment advances for multiple myeloma (MM) that have prolonged survival emphasise the importance of measuring patients' health-related quality of life (HRQoL) in clinical studies. HRQoL/functioning and symptoms of patients with relapsed/refractory MM (RRMM) receiving second- or third-line lenalidomide or bortezomib treatment were measured in a prospective European multicentre, observational study at different time points. At baseline, patients in the lenalidomide cohort were frailer than in the bortezomib cohort with more rapid disease progression at study entry (more patients with Eastern Cooperative Oncology Group performance status >2, shorter time from diagnosis, more chronic heart failure, higher serum creatinine levels, more patients with dialysis required)...
March 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28301380/nitroxoline-shows-antimyeloma-activity-by-targeting-the-trim25-p53-axle
#3
Hongwu Mao, Yanyun Du, Zubin Zhang, Biyin Cao, Jun Zhao, Haibin Zhou, Xinliang Mao
The aim of this study was to identify the most potent quinoline-based anti-infectives for the treatment of multiple myeloma (MM) and to understand the molecular mechanisms. A small-scale screen against a panel of marketed quinoline-based drugs was performed in MM cell lines. Cell apoptosis was examined by flow cytometry. Anti-MM activity was also evaluated in nude mice. Western blotting was performed to investigate mechanisms. Nitroxoline (NXQ) was the most effective in suppressing MM cell proliferation. NXQ induced more than 40% MM cell apoptosis within 24 h and potentiated anti-MM activities of current major drugs including doxorubicin and lenalidomide...
April 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28295729/targeting-of-b-cell-receptor-signalling-in-b-cell-malignancies
#4
M Jerkeman, M Hallek, M Dreyling, C Thieblemont, E Kimby, L Staudt
Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma...
March 14, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28295190/phase-i-study-of-cord-blood-derived-natural-killer-cells-combined-with-autologous-stem-cell-transplantation-in-multiple-myeloma
#5
Nina Shah, Li Li, Jessica McCarty, Indreshpal Kaur, Eric Yvon, Hila Shaim, Muharrem Muftuoglu, Enli Liu, Robert Z Orlowski, Laurence Cooper, Dean Lee, Simrit Parmar, Kai Cao, Catherine Sobieiski, Rima Saliba, Chitra Hosing, Sairah Ahmed, Yago Nieto, Qaiser Bashir, Krina Patel, Catherine Bollard, Muzaffar Qazilabsh, Richard Champlin, Katy Rezvani, Elizabeth J Shpall
Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantation (auto-HCT). Patients received lenalidomide (10 mg) on days -8 to -2, melphalan 200 mg/m(2) on day -7, CB-NK cells on day -5 and auto-HCT on day 0. Twelve patients were enrolled, three on each of four CB-NK cell dose levels: 5 × 10(6) , 1 × 10(7) , 5 × 10(7) and 1 × 10(8) CB-NK cells/kg...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28290121/population-pharmacokinetic-analysis-of-ixazomib-an-oral-proteasome-inhibitor-including-data-from-the-phase-iii-tourmaline-mm1-study-to-inform-labelling
#6
Neeraj Gupta, Paul M Diderichsen, Michael J Hanley, Deborah Berg, Helgi van de Velde, R Donald Harvey, Karthik Venkatakrishnan
Ixazomib is an oral proteasome inhibitor, approved in USA, Canada, Australia and Europe in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. We report a population pharmacokinetic model-based analysis for ixazomib that was pivotal in describing the clinical pharmacokinetics of ixazomib, to inform product labelling. Plasma concentration-time data were collected from 755 patients who received oral or intravenous ixazomib in once- or twice-weekly schedules in ten trials, including the global phase III TOURMALINE-MM1 study...
March 13, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28288710/possible-novel-agents-in-marginal-zone-lymphoma
#7
REVIEW
Pier Luigi Zinzani, Alessandro Broccoli
Efficacy, safety and mechanisms of action of novel agents in marginal zone lymphoma patients, both with a nodal and extranodal presentation, are reviewed. Data on lenalidomide, bortezomib and (90)yttrium-ibrutumomab tiuxetan are obtained from trials specifically designed for patients affected by marginal zone lymphoma and with various disease presentations. The role of targeted agents, such as obinutuzumab, ibrutinib and idelalisib, and of some very new drugs (venetoclax, copanlisib, ublituximab and TGR-1202) is also discussed, taking into account the most relevant experiences in patients with indolent non-Hodgkin's lymphomas...
March 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/28286633/successful-intrathecal-chemotherapy-combined-with-radiotherapy-followed-by-pomalidomide-and-low-dose-dexamethasone-maintenance-therapy-for-a-primary-plasma-cell-leukemia-patient
#8
Yusuke Yamashita, Shinobu Tamura, Takehiro Oiwa, Hiroshi Kobata, Kodai Kuriyama, Toshiki Mushino, Shogo Murata, Hiroki Hosoi, Akinori Nishikawa, Nobuyoshi Hanaoka, Takashi Sonoki
Primary plasma cell leukemia (PPCL) is a rare aggressive variant of plasma cell disorder and frequently presents with extramedullary disease. Central nervous system (CNS) involvement with PPCL has an extremely poor prognosis. We describe a 46-year-old man with PPCL treated with a combination of lenalidomide, bortezomib, and dexamethasone as induction therapy following upfront allogeneic stem cell transplantation (allo-SCT). Despite achieving a very good partial response, the patient suffered from an isolated CNS relapse 12 months after allo-SCT...
February 23, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28285081/a-phase-i-trial-of-high-dose-lenalidomide-and-melphalan-as-conditioning-for-autologous-stem-cell-transplantation-in-relapsed-or-refractory-multiple-myeloma
#9
Tomer M Mark, Danielle Guarneri, Peter Forsberg, Adriana Rossi, Roger Pearse, Arthur Perry, Karen Pekle, Linda Tegnestam, June Greenberg, Tsiporah Shore, Usama Gergis, Sebastian Mayer, Koen Van Besien, Scott Ely, David Jayabalan, Daniel Sherbenou, Morton Coleman, Ruben Niesvizky
Autologous stem cell transplantation (ASCT) conditioned with high-dose chemotherapy has long been established as the standard of care for eligible patients with newly diagnosed multiple myeloma. In spite of recent therapeutic advances, high-dose melphalan (HDM) remains the chemotherapy regimen of choice in this setting. Lenalidomide (LEN) in combination with low-dose dexamethasone is recognized as a standard of care for patients with relapsed or refractory multiple myeloma (RRMM), and there is growing support for the administration of LEN as maintenance therapy post-ASCT...
March 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28278713/lenalidomide-associated-progressive-multifocal-leukoencephalopathy
#10
Francesco Brigo, Elisabetta Pagani, Frediano Tezzon, Elisa Masi, Raffaele Nardone
No abstract text is available yet for this article.
February 21, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28278708/myelodysplastic-syndrome-with-concomitant-del-5q-and-jak2-v617f-mutation-transformed-to-acute-myeloid-leukemia-with-an-additional-chromosomal-abnormality-after-a-long-term-treatment-with-lenalidomide
#11
https://www.readbyqxmd.com/read/28277851/management-of-lower-risk-myelodysplastic-syndromes-without-del5q-current-approach-and-future-trends
#12
Maximilian Stahl, Amer M Zeidan
Myelodysplastic syndromes (MDS) are characterized by progressive bone marrow failure manifesting as blood cytopenia and a variable risk of progression into acute myeloid leukemia. MDS is heterogeneous in biology and clinical behavior. MDS is generally divided into lower-risk (LR) or higher-risk (HR) MDS. Goals of care in HR-MDS is changing the natural history of the disease, whereas in LR-MDS it is symptom control and quality of life. Areas covered: We review the epidemiology, tools of risk assessment, and the available therapeutic modalities for LR-MDS...
February 21, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28273193/-drug-therapy-of-lymphomas
#13
Lajos Gergely
The therapy of lymphomas has undergone a major expansion during the last decade. Novel therapeutic targets have appeared beyond classical chemotherapeutic combinations. These novel drugs have very pronounced action across lymphoma types, and their toxicity profile is usually better tolerable compared to standard chemotherapies. These new therapies are enabling us to offer treatment to those patients who have refractory disease, and we had no option to treat them before these drugs. The author describes several new therapeutic options...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28270494/blockade-of-deubiquitylating-enzyme-usp1-inhibits-dna-repair-and-triggers-apoptosis-in-multiple-myeloma-cells
#14
Deepika Sharma Das, Abhishek Das, Arghya Ray, Yan Song, Mehmet K Samur, Nikhil C Munshi, Dharminder Chauhan, Kenneth C Anderson
PURPOSE: The ubiquitin proteasome pathway is a validated therapeutic target in multiple myeloma (MM). Deubiquitylating enzyme USP1 participates in DNA damage response and cellular differentiation pathways. To date, the role of USP1 in MM biology is not defined. In the present study, we investigated the functional significance of USP1 in MM using genetic and biochemical approaches. EXPERIMENTAL DESIGN: To investigate the role of USP1 in myeloma, we utilized USP1 inhibitor SJB3-019A (SJB) for studies in myeloma cell lines and patient MM cells...
March 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28264055/enhancement-of-pomalidomide-anti-tumor-response-with-acy-241-a-selective-hdac6-inhibitor
#15
Brian J North, Ingrid Almeciga-Pinto, David Tamang, Min Yang, Simon S Jones, Steven N Quayle
Thalidomide-based Immunomodulatory Drugs (IMiDs®), including lenalidomide and pomalidomide, are effective therapeutics for multiple myeloma. These agents have been approved with, or are under clinical development with, other targeted therapies including proteasome inhibitors, αCD38 monoclonal antibodies, as well as histone deacetylase (HDAC) inhibitors for combination therapy. HDAC inhibitors broadly targeting Class I and IIb HDACs have shown potent preclinical efficacy but have frequently demonstrated an undesirable safety profile in combination therapy approaches in clinical studies...
2017: PloS One
https://www.readbyqxmd.com/read/28260960/clinical-hematological-and-cytogenetic-profile-of-adult-myelodysplastic-syndrome-in-a-tertiary-care-center
#16
Santhosh Narayanan
BACKGROUND: Myelodysplastic syndrome (MDS), a disorder of clonal hematopoiesis, is an important clinical entity, but most of the studies available are conducted among the Western population. Its etiological factors and clinicohematological profile in the Indian population are quite diverse. The information regarding its prognostic factors and cytogenetics is very scarce. OBJECTIVES: (1) To assess the clinicohematological profile, cytogenetics, prognostic factors, and outcome of MDS and (2) to study its progression to acute myeloid leukemia (AML) in the selected patients over the study period...
2017: Journal of Blood Medicine
https://www.readbyqxmd.com/read/28256432/phase-ii-study-of-dose-attenuated-bortezomib-cyclophosphamide-and-dexamethasone-vcd-lite-in-very-old-or-otherwise-toxicity-vulnerable-adults-with-newly-diagnosed-multiple-myeloma
#17
Sascha A Tuchman, Joseph O Moore, Carlos D DeCastro, Zhiguo Li, Emily Sellars, Yubin Kang, Gwynn Long, Cristina G Gasparetto
OBJECTIVES: Multiple myeloma (MM) primarily strikes older adults, but full-dose chemotherapy such as bortezomib (Velcade), cyclophosphamide and dexamethasone (VCD) is often excessively toxic to very old or frail adults and those with substantial comorbidities. We piloted dose-attenuated VCD ("VCD-Lite") in such vulnerable adults with newly diagnosed MM (NDMM). MATERIALS AND METHODS: Subjects with NDMM and a high risk of therapy-related toxicity due to factors above received bortezomib 1...
February 27, 2017: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/28252625/-light-chain-deposition-disease-is-a-hematologic-problem
#18
I G Rekhtina, L P Mendeleeva, L S Biryukova
AIM: To analyze clinical and laboratory data and treatment results in patients with light-chain deposition disease (LCDD). SUBJECTS AND METHODS: Nine patients with LCDD and kidney injury were examined. The diagnosis was based on the results of light and immunofluorescence microscopy of renal biopsy specimens. All the patients received bortezomib, cyclophosphamide, and dexamethasone (VCD) induction therapy. RESULTS: Six patients were diagnosed with multiple myeloma; in 3 patients LCDD was considered within monoclonal gammopathy manly involving the kidney...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28249894/targeting-cd38-suppresses-induction-and-function-of-t-regulatory-cells-to-mitigate-immunosuppression-in-multiple-myeloma
#19
Xiaoyan Feng, Li Zhang, Chirag Acharya, Gang An, Kenneth Wen, Luqui Qiu, Nikhil C Munshi, Yu-Tzu Tai, Kenneth C Anderson
PURPOSE: We study CD38 levels in immunosuppressive CD4+CD25highFoxp3+ Tregs and further define immune modulating effects of a therapeutic CD38 monoclonal antibody (mAb) Isatuximab (Isa)/SAR650984 in multiple myeloma (MM). EXPERIMENTAL DESIGN: We evaluated percentages of CD38-expressing subsets in Tregs from normal donors and MM patients. PBMCs were then treated with Isa with or without Lenalidomide (Len) or Pomalidomide (Pom) to identify their impact on percentage and immunosuppressive activity of Tregs on CD4+CD25- T cells (Tcons)...
March 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28249893/fda-drug-approval-elotuzumab-in-combination-with-lenalidomide-and-dexamethasone-for-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#20
Nicole J Gormley, Chia-Wen Ko, Albert Deisseroth, Lei Nie, Edvardas Kaminskas, Natasha Kormanik, Kirsten B Goldberg, Ann T Farrell, Richard Pazdur
On November 30, 2015, the U.S. Food and Drug Administration (FDA) approved elotuzumab (Empliciti, Bristol-Myers Squibb) in combination with lenalidomide and dexamethasone for treatment of patients with multiple myeloma who received one to three prior therapies. FDA approval was based primarily on results of a phase 3, randomized, open-label, multicenter trial, CA204004, that evaluated elotuzumab in combination with lenalidomide and dexamethasone (E-Ld), compared with lenalidomide and dexamethasone (Ld) alone, in patients with relapsed or refractory multiple myeloma...
March 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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