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https://www.readbyqxmd.com/read/28819709/use-of-direct-oral-anticoagulants-in-patients-on-immunomodulatory-agents
#1
L Man, A Morris, J Brown, S Palkimas, K Davidson
Immunomodulatory agents (IMiDs) are used to treat multiple hematologic malignancies. Their use is also associated with increased risk of venous thromboembolism (VTE). Direct oral anticoagulants (DOACs) have been increasingly utilized but due to their relative novelty, their role in malignancy has only been recently investigated. The objective of this study was to assess the safety and efficacy of DOACs in patients receiving IMiDs. This was a retrospective study of patients at our institution treated with an IMiD and concomitant warfarin or DOAC between January 1, 2010 and December 31, 2015...
August 17, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28781837/carfilzomib-and-dexamethasone-for-extramedullary-myeloma-with-pleuropericardial-involvement
#2
Ignacio Español, Marta Romera, María Dolores Gutiérrez-Meca, Maria Del Carmen García, Aurelia Tejedor, Antonio Martínez, Jerónima Ibáñez, Felipe De Arriba, Alfredo Minguela, Teodoro Iturbe, Maria Dolores López
The dismal outcome of pleuropericardial extramedullary multiple myeloma (EMM) reflects both the selection of resistant disease and absence of useful drugs. Carfilzomib and dexamethasone should be explored in advanced EMM patients, even for bortezomib-resistant patients, as may provide much longer overall survival than previously reported treatments.
August 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28763310/elderly-patients-with-multiple-myeloma-towards-a-frailty-approach
#3
Sonja Zweegman, Monika Engelhardt, Alessandra Larocca
PURPOSE OF REVIEW: To describe how to better identify frail multiple myeloma patients and to treat them appropriately. RECENT FINDINGS: Proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib, and immunomodulatory agents (IMiDs), such as thalidomide, lenalidomide, and pomalidomide, have significantly improved the outcome of multiple myeloma patients in the last decade. However, both in clinical trials and in daily clinical practice, elderly multiple myeloma patients have shown lesser benefit...
September 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28760601/a-functional-drug-re-purposing-screening-identifies-carfilzomib-as-a-drug-preventing-17%C3%AE-estradiol-er%C3%AE-signaling-and-cell-proliferation-in-breast-cancer-cells
#4
Claudia Busonero, Stefano Leone, Cinzia Klemm, Filippo Acconcia
Most cases of breast cancer (BC) are estrogen receptor α-positive (ERα+) at diagnosis. The presence of ERα drives the therapeutic approach for this disease, which often consists of endocrine therapy (ET). 4OH-Tamoxifen and faslodex (i.e., fulvestrant - ICI182,780) are two ETs that render tumor cells insensitive to 17β-estradiol (E2)-dependent proliferative stimuli and prevent BC progression. However, ET has limitations and serious failures in different tissues and organs. Thus, there is an urgent need to identify novel drugs to fight BC in the clinic...
July 29, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28747580/emerging-drugs-and-combinations-to-treat-multiple-myeloma
#5
REVIEW
Alessandra Larocca, Roberto Mina, Francesca Gay, Sara Bringhen, Mario Boccadoro
In the past few years, multiple targeted therapies and immunotherapies including second generation immunomodulatory drugs (pomalidomide) and proteasome inhibitors (carfilzomib, ixazomib), monoclonal antibodies and checkpoint inhibitors were approved for the treatment of myeloma or entered advanced phases of clinical testing. These agents showed significant activity in advanced myeloma and increased the available treatment strategies.Pomalidomide is well-tolerated and effective in patients with relapsed/refractory multiple myeloma who have exhausted any possible treatment with lenalidomide and bortezomib...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747306/how-i-treat-new-agents-in-myeloma
#6
Philippe Moreau
At present, multiple classes of agents with distinct mechanisms of action are available for the treatment of patients with multiple myeloma (MM), including alkylators, steroids, immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), histone deacetylase inhibitors (DACIs) and monoclonal antibodies (mAbs). Over the last 5 years, several new agents, such as the third-generation IMiD pomalidomide, the second generation PIs carfilzomib and ixazomib, the DACI panobinostat and two monoclonal antibodies, elotuzumab and daratumumab, have been approved, incorporated into clinical guidelines and have transformed our approach to the treatment of patients...
July 26, 2017: Blood
https://www.readbyqxmd.com/read/28723635/meta-analysis-of-the-efficacy-of-treatments-for-newly-diagnosed-and-relapsed-refractory-multiple-myeloma-with-del-17p
#7
Jinghua Liu, Hui Yang, Xiaochan Liang, Yuxin Wang, Jian Hou, Yanqin Liu, Jigang Wang, Fan Zhou
We analyzed the treatment of newly diagnosed and relapsed/refractory multiple myeloma (NDMM/RRMM) patients with del(17p). Thirteen prospective studies that evaluated 3,187 MM patients, including 685with del(17p), were included in our meta-analysis. The incidence of del(17p) in NDMM and RRMM patients was similar (13% vs. 14%, respectively, P = 0.64, I2 = 94%). The overall response rate (ORR) to new agents was 40.5% and 67.1%, respectively, in RRMM patients with or without del(17p) (P = 0.1, I2 = 63.9%). NDMM patients with del(17p) treated with PAD (bortezomib, adriamycin, and dexamethasone) induction therapy followed by bortezomib maintenance therapy had higher progression-free survival (PFS) (25...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28685863/efficacy-and-tolerability-of-the-histone-deacetylase-inhibitor-panobinostat-in-clinical-practice
#8
Marc-Andrea Baertsch, Jens Hillengass, Joanna Blocka, Stefan Schönland, Ute Hegenbart, Hartmut Goldschmidt, Marc S Raab
The histone deacetylase inhibitor panobinostat has shown efficacy in phase-II and phase-III trials for multiple myeloma and has recently received market approval in combination with bortezomib and dexamethasone. Here, we retrospectively report our single center experience with panobinostat/bortezomib/dexamethasone (FVD) in a heavily pretreated patient population (n = 24) with a high degree of refractoriness to proteasome inhibitors (PI) and immunomodulatory drugs (IMiD). Median age was 67 years (range 49-87) and the median number of prior therapies was 5 (range 2-17)...
July 7, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28680953/the-cost-impact-of-lenalidomide-for-newly-diagnosed-multiple-myeloma-in-the-eu5
#9
Steve Schey, Luis Felipe Casado Montero, Chloe Stengel-Tosetti, Craig J Gibson, Sujith Dhanasiri
INTRODUCTION: Lenalidomide is an active agent that was approved for use in the EU in 2015 as a first-line therapy for previously untreated, non-transplant eligible multiple myeloma patients. Our objective was to assess the cost impact of lenalidomide when selected as a first-line treatment for transplant-ineligible patients in France, Germany, Italy, Spain, and the United Kingdom (EU5). METHODS: We developed a cost-impact model of the total costs associated with newly diagnosed multiple myeloma over 5 years in the EU5 based on treatment duration and time to progression (TTP) (taken from trial data)...
2017: Oncology and Therapy
https://www.readbyqxmd.com/read/28679737/how-i-treat-first-relapse-of-myeloma
#10
Jean Luc Harousseau, Michel Attal
The standard treatment of relapsed multiple myeloma (MM) was either lenalidomide-dexamethasone (RD) or bortezomib-dexamethasone (VD) but it is changing rapidly for two reasons. Firstly lenalidomide and bortezomib are currently used in frontline treatment and many patients become resistant to these agents early in the course of their disease. Secondly six second-line new agents have been recently developed and offer new possibilities (pomalidomide, carfilzomib and ixazomib, panobinostat, elotuzumab and daratumumab)...
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28676669/carfilzomib-resistance-due-to-abcb1-mdr1-overexpression-is-overcome-by-nelfinavir-and-lopinavir-in-multiple-myeloma
#11
A Besse, S C Stolze, L Rasche, N Weinhold, G J Morgan, M Kraus, J Bader, H S Overkleeft, L Besse, C Driessen
Proteasome inhibitor carfilzomib has activity superior to bortezomib and is increasingly incorporated in multiple myeloma (MM) frontline therapy and relapsed settings. Most MM patients ultimately experience proteasome inhibitor-refractory disease, an unmet medical need with poorly understood biology and dismal outcome. Pharmacologic targeting of ABCB1 improved patient outcomes, including MM, but suffered from adverse drug effects and insufficient plasma concentrations. Proteomics analysis identified ABCB1 overexpression as the most significant change in carfilzomib-resistant MM cells...
July 5, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28670693/cxcl12-and-cxcr7-are-relevant-targets-to-reverse-cell-adhesion-mediated-drug-resistance-in-multiple-myeloma
#12
Johannes M Waldschmidt, Anna Simon, Dagmar Wider, Stefan J Müller, Marie Follo, Gabriele Ihorst, Sarah Decker, Joschka Lorenz, Manik Chatterjee, Abdel K Azab, Justus Duyster, Ralph Wäsch, Monika Engelhardt
Cell adhesion-mediated drug resistance (CAM-DR) by the bone marrow (BM) is fundamental to multiple myeloma (MM) propagation and survival. Targeting BM protection to increase the efficacy of current anti-myeloma treatment has not been extensively pursued. To extend the understanding of CAM-DR, we hypothesized that the cytotoxic effects of novel anti-myeloma agents may be abrogated by the presence of BM stroma cells (BMSCs) and restored by addition of the CXCL12 antagonist NOX-A12 or the CXCR4 inhibitor plerixafor...
July 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28665416/a-gene-expression-signature-distinguishes-innate-response-and-resistance-to-proteasome-inhibitors-in-multiple-myeloma
#13
A K Mitra, T Harding, U K Mukherjee, J S Jang, Y Li, R HongZheng, J Jen, P Sonneveld, S Kumar, W M Kuehl, V Rajkumar, B Van Ness
Extensive interindividual variation in response to chemotherapy is a major stumbling block in achieving desirable efficacy in the treatment of cancers, including multiple myeloma (MM). In this study, our goal was to develop a gene expression signature that predicts response specific to proteasome inhibitor (PI) treatment in MM. Using a well-characterized panel of human myeloma cell lines (HMCLs) representing the biological and genetic heterogeneity of MM, we created an in vitro chemosensitivity profile in response to treatment with the four PIs bortezomib, carfilzomib, ixazomib and oprozomib as single agents...
June 30, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28661711/safety-of-ixazomib-for-the-treatment-of-multiple-myeloma
#14
REVIEW
Antoine Bonnet, Philippe Moreau
Despite a major positive impact of proteasome inhibitors (PI), such as bortezomib and carfilzomib, on the survival of patients with multiple myeloma (MM) over the last few years, their use in clinical practice is limited by the development of drug resistance, significant side-effects or constraining administration schedules. Ixazomib is the first, and for now the only, oral PI, which was approved by the US Food and Drug Administration in 2015 and by the European Medicines Agency in 2016. Areas covered: In this review, we provide an overview of the preclinical and early-phase studies of ixazomib used as single-agent and in combination...
August 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28620163/natural-history-of-relapsed-myeloma-refractory-to-immunomodulatory-drugs-and-proteasome-inhibitors-a-multicenter-imwg-study
#15
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/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/28596644/highlights-of-multiple-myeloma-at-the-annual-meeting-of-american-society-of-hematology-2016
#17
REVIEW
Nidhi Tandon, Shaji K Kumar
This review discusses the landmark studies in the field of multiple myeloma (MM) which were presented at American society of hematology annual meeting, 2016. There were contrary results from two large phase III trials (one from US and one from Europe) that evaluated the role of additional interventions like tandem autologous transplant (ASCT) and consolidation after induction therapy followed by ASCT in newly diagnosed MM (NDMM) patients, but there were critical differences between the two studies. Novel agents like carfilzomib and ixazomib proved to be of benefit when used as induction and post ASCT consolidation and maintenance in NDMM...
June 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28592170/current-options-to-manage-waldenstr%C3%A3-m-s-macroglobulinemia
#18
Giulia Benevolo, Maura Nicolosi, Elisa Santambrogio, Umberto Vitolo
Waldenström's macroglobulinemia (WM) is a rare, incurable B-cell lymphoma, with a median survival of 5-10 years in symptomatic patients. There is no consensus on the standard of care and several agents are currently used in these patients. Areas covered: In this article, we will review the use of standard therapies and new drugs investigated such as monoclonal antibodies, proteasome inhibitors, immunomodulatory agents, Bruton's tyrosine kinase inhibitors and novel agents in early-stage development. Expert commentary: RCD (Rituximab/Cyclophosphamide/Dexamethasone) is an effective and safe treatment in first line in WM...
June 19, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28587834/spasmogenic-effects-of-the-proteasome-inhibitor-carfilzomib-on-coronary-resistance-vascular-tone-and-reactivity
#19
Carol Chen-Scarabelli, Giovanni Corsetti, Evasio Pasini, Francesco S Dioguardi, Gagan Sahni, Jagat Narula, Mara Gavazzoni, Hemang Patel, Louis Saravolatz, Richard Knight, Riccardo Raddino, Tiziano M Scarabelli
BACKGROUND: Carfilzomib (CFZ) is a new proteasome inhibitor used for the treatment of multiple myeloma. Besides heart failure, angina and myocardial ischemia occurred following administration of CFZ, which is not contraindicated in patients with recent myocardial infarction/unstable angina excluded from the safety trials. AIM OF STUDY: To test the effects of CFZ (10(-9) to 10(-7)mol/L) on vascular tone and reactivity in the isolated rabbit heart and aorta. METHODS AND RESULTS: CFZ administered by bolus injection to the isolated heart increased coronary perfusion pressure (CPP) at all tested concentrations and mildly raised left ventricular pressure and heart rate, only at the highest concentration...
July 2017: EBioMedicine
https://www.readbyqxmd.com/read/28583038/carfilzomib-as-salvage-therapy-in-waldenstrom-macroglobulinemia-a-case-series
#20
David H Vesole, Joshua Richter, Noa Biran, Laura McBride, Palka Anand, Mei Huang, Anita-Zahlten Kumeli, Zandra Klippel, Karim Iskander, David S Siegel
No abstract text is available yet for this article.
June 5, 2017: Leukemia & Lymphoma
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