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T Harada, H Miki, Q Cui, A Oda, R Amachi, J Teramachi, A Bat-Erdene, K Sogabe, M Iwasa, S Fujii, S Nakamura, K Kagawa, S Yoshida, I Endo, K Aihara, S Ozaki, T Matsumoto, M Abe
Leukemia accepted article preview online, 04 October 2016. doi:10.1038/leu.2016.273.
October 4, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Paola Neri, Nizar J Bahlis, Claudia Paba-Prada, Paul Richardson
Survival outcomes of patients with Multiple Myeloma (MM) have improved over the last decade due to the introduction of novel agents such as the immunomodulatory drugs thalidomide, lenalidomide (Len) and pomalidomide, and the proteasome inhibitors bortezomib (BTZ) and carfilzomib [1, 2]. However, despite these major advances, MM remains largely incurable and almost all patients relapse and require additional therapy [3]. The successful introduction of next generation novel agents including oral proteasome inhibitors, deacetylase inhibitors, and especially monoclonal antibodies as part of immunotherapy promises to further improve outcome...
2016: Cancer Treatment and Research
Kambis Sadeghi, Lukas Wisgrill, Isabelle Wessely, Susanne C Diesner, Simone Schüller, Celia Dürr, Armando Heinle, Monika Sachet, Arnold Pollak, Elisabeth Förster-Waldl, Andreas Spittler
Toll-like receptors (TLR) are crucial sensors of microbial agents such as bacterial or viral compounds. These receptors constitute key players in the induction of inflammation, e.g. in septic or chronic inflammatory diseases. Colony-stimulating factors (CSFs) such as granulocyte-macrophage-CSF (GM-CSF) or granulocyte-CSF (G-CSF) have been extensively investigated in their capacity to promote myelopoiesis in febrile neutropenia or to overcome immunosuppression in patients suffering from sepsis-associated neutropenia or from monocytic immunoincompetence...
2016: PloS One
Peter M Voorhees, Saad Z Usmani
The advent of the immunomodulatory drugs thalido-mide, lenalidomide, and pomalidomide; the proteasome inhib-itors bortezomib, carfilzomib, and ixazomib; the histone deacet-ylase inhibitor panobinostat; and the monoclonal antibodies elotuzumab and daratumumab has led to dramatic improvements in outcomes for patients with multiple myeloma. Along with progress in nontransplant therapy have come questions regarding the continued role of high-dose melphalan (HDM) supported by autologous stem cell transplant (ASCT) in the treatment of multiple myeloma...
September 2016: Clinical Advances in Hematology & Oncology: H&O
Lisa A Raedler
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
Priscila H Goncalves, Joseph Ziegelbauer, Thomas S Uldrick, Robert Yarchoan
PURPOSE OF REVIEW: This review discusses the pathogenesis and recent advances in the management of Kaposi sarcoma herpesvirus (KSHV)-associated diseases. RECENT FINDINGS: KSHV, a gammaherpesvirus, causes several tumors and related diseases, including Kaposi sarcoma, a form of multicentric Castleman disease (KSHV-MCD), and primary effusion lymphoma. These most often develop in patients infected with human immunodeficiency virus (HIV). KSHV-associated inflammatory cytokine syndrome (KICS) is a newly described syndrome with high mortality that has inflammatory symptoms-like MCD but not the pathologic lymph node findings...
September 22, 2016: Current Opinion in HIV and AIDS
Maria Gavriatopoulou, Evangelos Terpos, Efstathios Kastritis, Meletios A Dimopoulos
INTRODUCTION: Renal impairment (RI) is one of the most common complication of multiple myeloma (MM). RI is present in almost 20% of MM patients at diagnosis and in 40%-50% of patients during the course of their disease. AREAS COVERED: Biology along with tools for diagnosis and management of RI are reported in this paper. Papers published in PubMed and reported abstracts up to May 2016 were used. EXPERT OPINION: Moderate and severe RI increases the risk of early death; thus rapid intervention and initiation of anti-myeloma treatment is essential and improves renal outcomes in RI patients...
September 27, 2016: Expert Opinion on Pharmacotherapy
Jing-Ya Wang, Ya-Ni Huang, Chong-Chi Chiu, David Tweedie, Weiming Luo, Chaim G Pick, Szu-Yi Chou, Yu Luo, Barry J Hoffer, Nigel H Greig, Jia-Yi Wang
No abstract text is available yet for this article.
2016: Journal of Neuroinflammation
Ho Sup Lee, Chang-Ki Min
Multiple myeloma is an incurable malignant plasma cell-originating cancer. Although its treatment outcomes have improved with the use of glucocorticoids, alkylating drugs, and novel agents, including proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), relapse remains a serious problem. Strategies to improve outcomes following autologous stem cell transplantation and frontline treatments in non-transplant patients include consolidation to intensify therapy and improve the depth of response and maintenance therapy to achieve long-term disease control...
September 2016: Korean Journal of Internal Medicine
Kaoru Torigoe, Naoki Nakayama, Hiroyuki Achiwa
No abstract text is available yet for this article.
September 2016: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
Istvan Majer, Gijs van de Wetering, Zoltan Polanyi, Arun Krishna, Elisabeth Gray, Anuja Roy
BACKGROUND: In the UK, the standard of care for patients with multiple myeloma who received ≥2 prior treatments is lenalidomide plus dexamethasone (LEN + DEX) and pomalidomide plus DEX (POM + DEX) (in Wales only). Recently, panobinostat plus bortezomib and DEX (PAN + BTZ + DEX) was licensed in this setting. The current study assessed the progression-free survival (PFS) and overall survival (OS) outcomes with PAN + BTZ + DEX versus LEN + DEX (primary comparator) and POM + DEX (exploratory comparator)...
August 22, 2016: Applied Health Economics and Health Policy
Stefanie Lindner, Jan Krönke
Thalidomide was sold in the 1950s as a sedative and was also used by pregnant women to treat morning sickness. It became notorious for causing severe birth defects and was removed from the market. More than four decades later, thalidomide had a renaissance in the treatment of cancer. Thalidomide and its more potent analogs, lenalidomide and pomalidomide, are nowadays approved treatments for multiple myeloma and myelodysplastic syndrome with deletion of chromosome 5q. In addition, thalidomide and its analogs inhibit release of tumor necrosis factor-α and increase interleukin-2 (IL-2) and interferon-γ release from T cells...
August 5, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Takahiro Murai, Norihito Kawashita, Yu-Shi Tian, Tatsuya Takagi
BACKGROUND: Thalidomide and its analogs, lenalidomide and pomalidomide (referred to as immunomodulatory imide drugs or IMiDs) have been known to treat multiple myeloma and other hematologic malignancies as well as to cause teratogenicity. Recently the protein cereblon was identified as the primary target of IMiDs, and crystallographic studies of the cereblon-IMiDs complex showed strong enantioselective binding for the (S)-enantiomer of IMiDs. RESULTS: Using the structures of cereblon and IMiDs [both (S)-enantiomers and (R)-enantiomers] we performed docking simulations in order to replicate this enantiomeric selectivity and to identify the region(s) contributing to this selectivity...
2016: SpringerPlus
Lisa Bloudek, Anuja Roy, Jonathan K Kish, David S Siegel, Sundar Jagannath, Denise Globe, Laurie Orloski, Emil T Kuriakose
BACKGROUND: Multiple myeloma is an incurable B-cell malignancy with a natural history that involves alternating periods of remission and subsequent relapse. For relapsed and/or refractory multiple myeloma (RRMM), the typical patient currently receives more lines of therapy than has been feasible in the past, translating into longer progression-free survival (PFS). Consequently, cost issues have become more prominent because patients may be offered newer and more expensive therapies during a more prolonged overall treatment course...
August 2016: Journal of Managed Care & Specialty Pharmacy
Yandun Zou, Xiaoyan Ma, Haiying Yu, Chunling Hu, Limei Fan, Xuehong Ran
PURPOSE: The use of carfilzomib/pomalidomide single-agent or in combination with other agents in patients with refractory/relapsed multiple myeloma (RRMM) was not clearly clarified in clinical practice. We sought to compile the available clinical reports to better understand the efficacy and safety of carfilzomib (CFZ) and pomalidomide (POM). RESULTS: Based on our research criteria, we identified 37 prospective studies that evaluated 1160 patients. Analysis of subgroup differences between carfilzomib single-agent and CFZ/DEX dual combination showed significantly(P < 0...
July 21, 2016: Oncotarget
Teresa Paíno, Antonio García-Gómez, Lorena González-Méndez, Laura San Segundo, Susana Hernández-García, Ana-Alicia López-Iglesias, Esperanza M Algarín, Montserrat Martín-Sánchez, David Corbacho-González, Carlos Ortiz-de-Solórzano, Luis Corchete, Norma C Gutiérrez, Maria Victoria Mateos, Mercedes Garayoa, Enrique M Ocio
PURPOSE: PIM kinases are a family of serine/threonine kinases recently proposed as therapeutic targets in oncology. In the present work, we have investigated the effects of the novel pan-PIM kinase inhibitor, PIM447, on myeloma cells and myeloma-associated bone disease using different preclinical models. EXPERIMENTAL DESIGN: In vitro/ex vivo cytotoxicity of PIM447 was evaluated on myeloma cell lines and patient samples. Synergistic combinations with standard treatments were analyzed with Calcusyn Software...
July 20, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Priya Sriskandarajah, Charlotte Pawlyn, Kabir Mohammed, Claire E Dearden, Faith E Davies, Gareth J Morgan, Kevin D Boyd, Martin F Kaiser
No abstract text is available yet for this article.
July 20, 2016: Leukemia & Lymphoma
Laura Breda, Irene Motta, Silvia Lourenco, Chiara Gemmo, Wulan Deng, Jeremy W Rupon, Osheiza Y Abdulmalik, Deepa Manwani, Gerd A Blobel, Stefano Rivella
Overcoming the silencing of the fetal γ-globin gene has been a long-standing goal in the treatment of sickle cell disease (SCD). The major transcriptional enhancer of the β-globin locus, called the locus control region (LCR), dynamically interacts with the developmental stage-appropriate β-type globin genes via chromatin looping, a process requiring the protein Ldb1. In adult erythroid cells, the LCR can be redirected from the adult β- to the fetal γ-globin promoter by tethering Ldb1 to the human γ-globin promoter with custom-designed zinc finger (ZF) proteins (ZF-Ldb1), leading to reactivation of γ-globin gene expression...
August 25, 2016: Blood
Vaishali Sanchorawala, Anthony C Shelton, Stephen Lo, Cindy Varga, J Mark Sloan, David C Seldin
The objectives of a phase 1/2 trial of pomalidomide with dexamethasone for the treatment of light chain (AL) amyloidosis were to determine the safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 dose, and hematologic and clinical response. A 3+3 dose-escalation phase (15 patients) was followed by an expansion cohort (12 patients) enrolled at the MTD. Pomalidomide was administered at 2 and 3 mg on days 1 to 28 (cohorts 1 and 2) and 4 mg on days 1 to 21 (cohort 3) every 28 days, with weekly dexamethasone at a dose of 20 mg...
August 25, 2016: Blood
Leonard Naymagon, Maher Abdul-Hay
Multiple myeloma (MM) is a disease that affects plasma cells and can lead to devastating clinical features such as anemia, lytic bone lesions, hypercalcemia, and renal disease. An enhanced understanding of MM disease mechanisms has led to new more targeted treatments. There is now a plethora of treatments available for MM. In this review article, our aim is to discuss many of the novel agents that are being studied or have recently been approved for the treatment of MM. These agents include the following: immunomodulators (pomalidomide), proteasome inhibitors (carfilzomib, marizomib, ixazomib, oprozomib), alkylating agents (bendamustine), AKT inhibitors (afuresertib), BTK inhibitors (ibrutinib), CDK inhibitors (dinaciclib), histone deacetylase inhibitors (panobinostat, rocilinostat, vorinostat), IL-6 inhibitors (siltuximab), kinesin spindle protein inhibitors (filanesib), monoclonal antibodies (daratumumab, elotuzumab, indatuximab, SAR650984), and phosphoinositide 3-kinase (PI3K) inhibitors...
2016: Journal of Hematology & Oncology
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