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Lenalidomide AND lymphoma

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https://www.readbyqxmd.com/read/29295936/gene-regulation-and-suppression-of-type-i-interferon-signaling-by-stat3-in-diffuse-large-b-cell-lymphoma
#1
Li Lu, Fen Zhu, Meili Zhang, Yangguang Li, Amanda C Drennan, Shuichi Kimpara, Ian Rumball, Christopher Selzer, Hunter Cameron, Ashley Kellicut, Amanda Kelm, Fangyu Wang, Thomas A Waldmann, Lixin Rui
STAT3 is constitutively activated in many cancers and regulates gene expression to promote cancer cell survival, proliferation, invasion, and migration. In diffuse large B cell lymphoma (DLBCL), activation of STAT3 and its kinase JAK1 is caused by autocrine production of IL-6 and IL-10 in the activated B cell-like subtype (ABC). However, the gene regulatory mechanisms underlying the pathogenesis of this aggressive lymphoma by STAT3 are not well characterized. Here we performed genome-wide analysis and identified 2,251 STAT3 direct target genes, which involve B cell activation, survival, proliferation, differentiation, and migration...
January 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29237802/phase-1-dose-escalation-study-of-anti-ctla-4-antibody-ipilimumab-and-lenalidomide-in-patients-with-advanced-cancers
#2
Divya Sakamuri, Isabella C Glitza, Sonia L Betancourt Cuellar, Vivek Subbiah, Siqing Fu, Apostolia M Tsimberidou, Jennifer J Wheler, David S Hong, Aung Naing, Gerald S Falchook, Michelle A Fanale, Maria E Cabanillas, Filip Janku
Preclinical data suggest that combining a check point inhibition with immunomodulatory derivative can increase anticancer response. We designed a dose escalation study using a 3+3 design to determine the safety, maximum tolerated dose (MTD) or recommended phase 2 dose (R2PD) and dose limiting toxicities (DLT) of the anti-CTLA-4 antibody ipilimumab (1.5-3mg/kg intravenously every 28 days x 4) and lenalidomide (10-25mg orally daily for 21 of 28 days until disease progression or unacceptable toxicity) in advanced cancers...
December 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29222281/improved-biological-insight-and-influence-on-management-in-indolent-lymphoma-talk-3-update-on-nodal-and-splenic-marginal-zone-lymphoma
#3
REVIEW
Catherine Thieblemont
Splenic marginal zone lymphoma (SMZL) and nodal marginal zone lymphoma (NMZL) are rare indolent chronic B-cell lymphomas. Prognosis is typically good with median survival around 10-15 years. Management is generally based on the presence of symptoms or high tumor burden. There are no standard treatments for these 2 entities, and therapeutic strategies are rapidly evolving. Clinical developments for these 2 entities are oriented by genomic studies, with largely overlapping mutational profiles involving the NOTCH, B-cell receptor (BcR) and nuclear factor κB (NF-κB) signaling, chromatin remodeling, and the cytoskeleton...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29212067/lenalidomide-maintenance-after-r-chop-therapy-in-diffuse-large-b-cell-lymphoma-can-it-be-a-standard-of-care
#4
Reyad Dada
Diffuse large B-cell lymphoma is an aggressive non-Hodgkin lymphoma subtype which requires immediate treatment. Standard treatment is usually a combined immune chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Since R-CHOP was approved, several attempts to combine it with novel agents and/or use them as maintenance therapy failed to improve the outcome. Recently, maintenance with lenalidomide after standard immune chemotherapy showed promising results. This review discusses the most pertinent published and running studies, analyzing study design, results, and practicality...
December 7, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/29193019/prospective-subgroup-analyses-of-the-randomized-mcl-002-sprint-study-lenalidomide-versus-investigator-s-choice-in-relapsed-or-refractory-mantle-cell-lymphoma
#5
Luca Arcaini, Thierry Lamy, Jan Walewski, David Belada, Jiri Mayer, John Radford, Wojciech Jurczak, Franck Morschhauser, Julia Alexeeva, Simon Rule, José Cabeçadas, Elias Campo, Stefano A Pileri, Tsvetan Biyukov, Meera Patturajan, Marie-Laure Casadebaig Bravo, Marek Trnĕný
In the mantle cell lymphoma (MCL)-002 study, lenalidomide demonstrated significantly improved median progression-free survival (PFS) compared with investigator's choice (IC) in patients with relapsed/refractory MCL. Here we present the long-term follow-up data and results of preplanned subgroup exploratory analyses from MCL-002 to evaluate the potential impact of demographic factors, baseline clinical characteristics and prior therapies on PFS. In MCL-002, patients with relapsed/refractory MCL were randomized 2:1 to receive lenalidomide (25 mg/day orally on days 1-21; 28-day cycles) or single-agent IC therapy (rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine)...
November 28, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29184450/coexisting-multiple-myeloma-lymphoma-and-non-small-cell-lung-cancer-a-case-report-and-review-of-the-literature
#6
Parth Khade, Srinivas Devarakonda
Multiple myeloma is a plasma cell dyscrasia characterized by neoplastic proliferation of plasma cells, producing a monoclonal immunoglobulin. Small lymphocytic lymphoma (SLL) is a neoplasm consisting of monoclonal B-cell lymphocyte proliferation. We present an extremely rare case of coexisting multiple myeloma, SLL, and squamous cell carcinoma of the lung in a 74-year-old female patient. She initially presented with a midline mass with pain in the lumbar area. Debulking surgery was performed, and pathology showed plasmacytoma...
2017: International Medical Case Reports Journal
https://www.readbyqxmd.com/read/29172868/treatment-for-patients-with-relapsed-refractory-mantle-cell-lymphoma-european-based-recommendations
#7
Martin Dreyling, Igor Aurer, Sergio Cortelazzo, Olivier Hermine, Georg Hess, Mats Jerkeman, Steven Le Gouill, Vincent Ribrag, Marek Trněný, Carlo Visco, Jan Walewski, Francesco Zaja, Pier Luigi Zinzani
Patients with mantle cell lymphoma (MCL) usually respond to initial combination chemotherapy, but the disease inevitably relapses and often follows an aggressive course. Here, clinical study results published since 2008 for patients with relapsed/refractory MCL were reviewed to compare available evidence for treatment guidance. Most trials identified were non-randomized, phase II studies performed at a limited number of sites, and many evaluated MCL as one of multiple non-Hodgkin lymphoma subtypes. Additional randomized, comparative trials are needed...
November 27, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29126866/advances-in-diagnosis-and-management-of-diffuse-large-b-cell-lymphoma
#8
REVIEW
Fernando Cabanillas, Bijal Shah
The management of diffuse large B-cell lymphoma (DLBCL) has been gradually evolving since the discovery of its 2 major forms, the germinal center B-like (GCB) and activated B-cell (ABC) types. Although the reference standard for the identification of these cell types is considered gene expression profiling (GEP), currently the only method commercially available is immunohistochemistry (IHC). The application of various IHC-based algorithms and their correlation with GEP and clinical outcome are discussed. Because of the adverse prognostic implications of the non-GCB type and its potential effects on treatment selection, the recently revised World Health Organization classification has included these biologic cell types...
December 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29096668/observational-study-of-lenalidomide-in-patients-with-mantle-cell-lymphoma-who-relapsed-progressed-after-or-were-refractory-intolerant-to-ibrutinib-mcl-004
#9
Michael Wang, Stephen J Schuster, Tycel Phillips, Izidore S Lossos, Andre Goy, Simon Rule, Mehdi Hamadani, Nilanjan Ghosh, Craig B Reeder, Evelyn Barnett, Marie-Laure Casadebaig Bravo, Peter Martin
BACKGROUND: The observational MCL-004 study evaluated outcomes in patients with relapsed/refractory mantle cell lymphoma who received lenalidomide-based therapy after ibrutinib failure or intolerance. METHODS: The primary endpoint was investigator-assessed overall response rate based on the 2007 International Working Group criteria. RESULTS: Of 58 enrolled patients (median age, 71 years; range, 50-89), 13 received lenalidomide monotherapy, 11 lenalidomide plus rituximab, and 34 lenalidomide plus other treatment...
November 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29066507/pqr309-is-a-novel-dual-pi3k-mtor-inhibitor-with-pre-clinical-antitumor-activity-in-lymphomas-as-a-single-agent-and-in-combination-therapy
#10
Chiara Tarantelli, Eugenio Gaudio, Alberto Jesus Arribas, Ivo Kwee, Petra Hillmann, Andrea Rinaldi, Luciano Cascione, Filippo Spriano, Elena Bernasconi, Francesca Guidetti, Laura Carrassa, Roberta Bordone Pittau, Florent Beaufils, Reto Ritschard, Denise Rageot, Alexander Sele, Barbara Dossena, Francesca M Rossi, Antonella Zucchetto, Monica Taborelli, Valter Gattei, Davide Rossi, Anastasios Stathis, Georg Stussi, Massimo Broggini, Matthias P Wymann, Andreas Wicki, Emanuele Zucca, Vladimir Cmiljanovic, Doriano Fabbro, Francesco Bertoni
PURPOSE: Activation of the PI3K/mTOR signaling pathway is recurrent in different lymphoma types and pharmacological inhibition of the PI3K/mTOR pathway has shown activity in lymphoma patients. Here, we extensively characterized the in vitro and in vivo activity and the mechanism of action of PQR309 (bimiralisib), a novel oral selective dual PI3K/mTOR inhibitor under clinical evaluation, in preclinical lymphoma models. EXPERIMENTAL DESIGN: This study included preclinical in vitro activity screening on a large panel of cell lines, both as single agent and in combination, validation experiments on in vivo models and primary cells, proteomics and gene expression profiling and comparison with other signaling inhibitors...
October 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29065744/exploring-the-potential-cost-effectiveness-of-precision-medicine-treatment-strategies-for-diffuse-large-b-cell-lymphoma
#11
Qiushi Chen, Ashley D Staton, Turgay Ayer, Daniel A Goldstein, Jean L Koff, Christopher R Flowers
Activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) is associated with worse survival after standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) chemoimmunotherapy compared to germinal center B-cell-like (GCB) subtype. Preliminary evidence suggests that benefits from novel agents may vary by subtype. Hypothesizing that treatment stratified by DLBCL subtype could be potentially cost-effective, we developed micro-simulation models to compare three first-line treatment strategies: (1) standard RCHOP for all patients (2) subtype testing followed by RCHOP for GCB and novel treatment for ABC DLBCL, and (3) novel treatment for all patients...
October 25, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29045503/maintenance-therapy-following-induction-chemoimmunotherapy-in-patients-with-diffuse-large-b-cell-lymphoma-current-perspective
#12
N M Reddy, C Thieblemont
Background: Maintenance therapy has proven efficacy in indolent non-Hodgkin lymphoma (NHL), yet its role in diffuse large B-cell lymphoma (DLBCL) is an area of ongoing investigation. While DLBCL is potentially curable, >30% of patients relapse following front-line therapy and have a poor prognosis, especially those with refractory disease. Maintenance therapy holds promise to maintain response post-induction. Patients and methods: Keyword searches were carried out in PubMed and congress abstracts of 'diffuse large B-cell lymphoma' and 'maintenance' and focused on phase II/III studies of maintenance following front-line induction...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28978850/recent-topics-in-imids-and-cereblon
#13
Takumi Ito, Hiroshi Handa
Immunomodulatory drugs (IMiDs) are a new class of anticancer compounds that are derived from thalidomide. Lenalidomide and pomalidomide are well-known IMiDs, and they have already been approved by FDA for the treatment of several diseases, including multiple myeloma. Cereblon (CRBN) is a common primary target for IMiDs. It works as a substrate receptor of CRL4. Accumulating evidence has shown that the substrate specificity of CRL4(CRBN) is altered by ligands such as IMiDs. Recently, novel CRBN-binding compounds have been developed and are called "cereblon modulators"...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28946015/peripheral-t-cell-lymphomas-focusing-on-novel-agents-in-relapsed-and-refractory-disease
#14
REVIEW
Alessandro Broccoli, Lisa Argnani, Pier Luigi Zinzani
Patients with relapsed or refractory peripheral T-cell lymphoma display a dismal prognosis and their therapy represents an unmet medical need, as the best treatment strategy is yet to be determined. Exciting data on novel targeted agents are now emerging from recently concluded and ongoing clinical trials in patients with relapsed and refractory PTCL. Four recently approved compounds are used as single agents: pralatrexate, a novel antifolate agent; romidepsin and belinostat, both histone deacetylase (HDAC) inhibitors; brentuximab vedotin, an anti-CD30 drug-conjugated monoclonal antibody...
November 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28945884/a-phase-ii-trial-of-lenalidomide-plus-rituximab-in-previously-untreated-follicular-non-hodgkin-s-lymphoma-nhl-calgb-50803-alliance
#15
P Martin, S-H Jung, B Pitcher, N L Bartlett, K A Blum, T Shea, E D Hsi, J Ruan, S E Smith, J P Leonard, B D Cheson
Background: This multicenter, phase II trial tested the tolerability and efficacy of lenalidomide plus rituximab in patients with previously untreated follicular lymphoma (FL). Patients and methods: Patients with grade 1-3a FL, stage 3-4 or bulky stage 2, FL international prognostic index (FLIPI) 0-2, and no prior therapy were eligible to receive rituximab 375 mg/m2 weekly during cycle 1 and day 1 of cycles 4, 6, 8, and 10, plus lenalidomide 20-25 mg on days 1-21 for twelve 28-day cycles...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28922238/primary-central-nervous-system-lymphoma-time-for-diagnostic-biomarkers-and-biotherapies
#16
Louis Royer-Perron, Khê Hoang-Xuan, Agusti Alentorn
PURPOSE OF REVIEW: Primary central nervous system lymphoma (PCNSL) is a rare cancer with a somber prognosis in older patients, which it affects predominantly. Only in recent years have molecular alterations characterizing PCNSL been thoroughly described. This opens possibilities for the use of targeted therapies. Developments in imaging and biomarkers have also great potential to help clinicians faced with diagnostic and prognostic uncertainties. RECENT FINDINGS: Several biomarkers for PCNSL, such as different microRNAs, which could be tested in cerebrospinal fluid and vitreous fluid, and IL-10, which has been shown to have excellent sensitivity and specificity in the cerebrospinal fluid, have emerged in the last years...
December 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28893618/lenalidomide-modulates-gene-expression-in-human-abc-dlbcl-cells-by-regulating-ikaros-interaction-with-an-intronic-control-region-of-spib
#17
Lauren A Solomon, Carolina R Batista, Rodney P DeKoter
Activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) is associated with a poor prognosis compared with other DLBCL types and therefore represents a top priority for developing novel therapies. Lenalidomide, an immunomodulatory drug in trials for treatment of ABC-DLBCL, targets the transcription factor IKAROS for degradation by the cereblon E3 ubiquitin ligase complex. In this study, we investigated whether the gene encoding the transcription factor SPI-B is a target of IKAROS. Using cultured ABC-DLBCL cell lines, we found that high levels of SPI-B expression conferred resistance to lenalidomide...
December 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28881567/restoration-of-immune-surface-molecules-in-kaposi-sarcoma-associated-herpes-virus-infected-cells-by-lenalidomide-and-pomalidomide
#18
David A Davis, Suraj Mishra, Holda A Anagho, Ashley I Aisabor, Prabha Shrestha, Victoria Wang, Yuki Takamatsu, Kenji Maeda, Hiroaki Mitsuya, Jerome B Zeldis, Robert Yarchoan
Kaposi sarcoma-associated herpesvirus (KSHV) is the cause of several tumors, including Kaposi sarcoma and primary effusion lymphoma (PEL). Most viruses have evolved means of escaping immune recognition. KSHV downregulates MHC-I expression during lytic infection, and expression of ICAM-1 and B7-2 (CD86) during latent infection, allowing evasion of T cell and natural killer immunity respectively. These effects are largely mediated by two KSHV-encoded proteins, K3 and K5. We show here that lenalidomide (Len) and pomalidomide (Pom) prevent down-regulation of MHC-I during lytic activation, and restore ICAM-1 and B7-2 surface expression in latently infected PEL cells...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28879716/concomitant-occurrence-of-blastic-plasmacytoid-dendritic-cell-neoplasm-and-acute-myeloid-leukaemia-after-lenalidomide-treatment-for
#19
Nicola S Fracchiolla, Alessanda Iurlo, Valeria Ferla, Bruno Fattizzo, Alessandra Freyrie, Gianluigi Reda, Agostino Cortelezzi
BACKGROUND: Myelodysplastic syndromes with chromosome 5 long arm deletion (5q-mds) may benefit from lenalidomide treatment. However, unresponsive patients have a high risk for clonal evolution and progression to acute myeloid leukemia. Case: We describe a 5q-patient treated with lenalidomide, who concomitantly developed acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm, a rare and highly aggressive lymphoma. CONCLUSIONS: Evolution of 5q- syndrome to acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm may have occurred through various mechanisms, including persistence of neoplastic lenalidomide-resistant stem cells and selection of a more aggressive clone via lenalidomide augmentation of the ARPC1B gene, or because of lenalidomide stimulation on dendritic cells...
September 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28874597/risk-of-febrile-neutropenia-associated-with-select-myelosuppressive-chemotherapy-regimens-in-a-large-community-based-oncology-practice
#20
Yanli Li, Leila Family, Su-Jau Yang, Zandra Klippel, John H Page, Chun Chao
Background: NCCN has classified commonly used chemotherapy regimens into high (>20%), intermediate (10%-20%), or low (<10%) febrile neutropenia (FN) risk categories based primarily on clinical trial evidence. Many chemotherapy regimens, however, remain unclassified by NCCN or lack FN incidence data in real-world clinical practice. Patients and Methods: We evaluated incidence proportions of FN and grade 4 and 3/4 neutropenia during the first chemotherapy course among patients from Kaiser Permanente Southern California who received selected chemotherapy regimens without well-established FN risk...
September 2017: Journal of the National Comprehensive Cancer Network: JNCCN
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