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https://www.readbyqxmd.com/read/28504554/how-is-patient-care-for-multiple-myeloma-advancing
#1
Sonja Genadieva Stavric, Francesca Bonello, Sara Bringhen, Mario Boccadoro, Alessandra Larocca
Treatment of multiple myeloma has undergone profound changes in the past years thanks to the increased understanding of the biology of the disease and the new treatment options. New drugs and effective approaches are currently available for the treatment of multiple myeloma, including immunomodulatory agents, proteasome inhibitors and autologous stem cell transplantation. Areas covered. We have described the recent updated criteria to start treatment in multiple myeloma and summarized clinical data from major studies including most recent agents...
May 15, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28495797/ixazomib-enhances-parathyroid-hormone-pth-induced-%C3%AE-catenin-t-cell-factor-tcf-signaling-by-dissociating-%C3%AE-catenin-from-the-pth-receptor
#2
Yanmei Yang, Hong Lei, Ya-Wei Qiang, Bin Wang
The anabolic action of PTH in bone is mostly mediated by cAMP/PKA and Wnt-independent activation of β-catenin/T-cell factor (TCF) signaling. β-catenin switches the PTH receptor (PTHR) signaling from cAMP/PKA to PLC/PKC activation by binding to the PTHR. Ixazomib (Izb) is the first orally administered proteasome inhibitor that was approved recently for the treatment of multiple myeloma in part through inhibition of pathologic bone destruction. Proteasome inhibitors were reported to stabilize β-catenin by ubiquitin-proteasome pathway...
May 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28485007/management-of-adverse-events-associated-with-ixazomib-plus-lenalidomide-dexamethasone-in-relapsed-refractory-multiple-myeloma
#3
Shaji Kumar, Philippe Moreau, Parameswaran Hari, Maria-Victoria Mateos, Heinz Ludwig, Chaim Shustik, Tamas Masszi, Andrew Spencer, Roman Hájek, Kenneth Romeril, Irit Avivi, Anna M Liberati, Monique C Minnema, Hermann Einsele, Sagar Lonial, Deborah Berg, Jianchang Lin, Neeraj Gupta, Dixie-Lee Esseltine, Paul G Richardson
The oral proteasome inhibitor ixazomib is approved in the United States, European Union and other countries, in combination with oral lenalidomide and dexamethasone (Rd), for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was based on the global, randomised, double-blind, placebo-controlled Phase III TOURMALINE-MM1 study of ixazomib-Rd (IRd) versus placebo-Rd in patients with relapsed/refractory multiple myeloma. IRd resulted in a significant improvement in progression-free survival versus placebo-Rd (median: 20·6 vs...
May 9, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28388244/which-therapies-will-move-to-the-front-line-for-multiple-myeloma
#4
María J Cejalvo, Javier de la Rubia
Despite substantial progress, multiple myeloma (MM) remains an incurable disease. Recently the availability of several novel drugs with different and innovative mechanisms of action (daratumumab, elotuzumab, carfilzomib, ixazomib, and panobinostat) has increased the therapeutic options but has also increased complexity in the management of patients with MM. Areas covered: The outstanding results observed in the relapsed setting with regimens including these new drugs has provided the investigators with several treatment options that are being tested also in patients with newly diagnosed MM...
April 24, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28347676/treating-multiple-myeloma-patients-with-oral-therapies
#5
REVIEW
Shaji K Kumar, Ravi Vij, Stephen J Noga, Deborah Berg, Lonnie Brent, Lawrence Dollar, Ajai Chari
Recent advances have highlighted the importance of long-term, continuous treatment in multiple myeloma (MM) to improve survival. However, treatment burden continues to negatively impact the real-world duration of MM therapy, and strategies to limit the adverse impact of treatment on patient quality of life are therefore particularly important. Oral MM therapies include the immunomodulatory drugs lenalidomide, thalidomide, and pomalidomide; the alkylating agents melphalan and cyclophosphamide; the histone deacetylase inhibitor panobinostat; the corticosteroids prednisone and dexamethasone; and the proteasome inhibitor ixazomib...
March 7, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28342223/ritonavir-and-ixazomib-kill-bladder-cancer-cells-by-causing-ubiquitinated-protein-accumulation
#6
Akinori Sato, Takako Asano, Kazuki Okubo, Makoto Isono, Tomohiko Asano
There is no curative treatment for advanced bladder cancer. Causing ubiquitinated protein accumulation and endoplasmic reticulum stress is a novel approach to cancer treatment. The HIV protease inhibitor ritonavir has been reported to suppress heat shock protein 90 and increase the amount of unfolded proteins in the cell. If the proteasome functions normally, however, they are rapidly degraded. We postulated that the novel proteasome inhibitor ixazomib combined with ritonavir would kill bladder cancer cells effectively by inhibiting degradation of these unfolded proteins and thereby causing ubiquitinated proteins to accumulate...
March 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28333868/proteasome-inhibitor-induced-gastrointestinal-toxicity
#7
Romany L Stansborough, Rachel J Gibson
PURPOSE OF REVIEW: Gastrointestinal toxicities are commonly reported following treatment with proteasome inhibitors. The first-generation proteasome inhibitor, bortezomib, induces significant gastrointestinal side effects including nausea, vomiting, diarrhoea, and constipation, occurring in up to 84% of patients. Despite the development of safer proteasome inhibitors, such as carfilzomib, gastrointestinal toxicities remain some of the most common side effects. This review aims to summarize the previous literature on proteasome inhibitor-induced gastrointestinal toxicities, report on recent updates in the field, and investigate possible mechanisms of this toxicity...
June 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28327055/the-evaluation-of-the-anti-cancer-activity-of-ixazomib-on-caco2-colon-solid-tumor-cells-comparison-with-bortezomib
#8
Selin Engür, Miriş Dikmen
Proteasome inhibition has recently emerged as a clinically effective anticancer therapeutic approach. The first proteasome inhibitor, bortezomib (Velcade, PS-341), and new proteasome inhibitors including ixazomib have become more important in the development of targeted cancer therapies. Under physiological conditions, MLN9708 (ixazomib citrate), the stable citrate ester drug substance, hydrolyzes rapidly to MLN2238 (ixazomib), the biologically active boronic acid. It is a second-generation proteasome inhibitor, similar to the well-known proteasome inhibitor bortezomib, which is currently being investigated in phase 3 trials as a treatment for multiple Myeloma...
March 22, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28325256/how-have-evolutions-in-strategies-for-the-treatment-of-relapsed-refractory-multiple-myeloma-translated-into-improved-outcomes-for-patients
#9
REVIEW
Pieter Sonneveld, Edwin De Wit, Philippe Moreau
Although multiple myeloma (MM) remains incurable, the introduction of novel agents has improved clinical outcomes dramatically over the past 15 years. Response rates have risen from ∼30% with single agents to up to 90% with combination therapies. The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, and the proteasome inhibitor bortezomib, form the foundations for treatment of relapsed and/or refractory MM (RRMM). Newer agents, such as the IMiD pomalidomide, the histone deacetylase inhibitor panobinostat and the proteasome inhibitors carfilzomib and ixazomib, as well as the monoclonal antibodies daratumumab and elotuzumab, have further improved overall response rates in these patients...
April 2017: Critical Reviews in Oncology/hematology
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
#10
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/28273193/-drug-therapy-of-lymphomas
#11
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/28205262/modern-multiple-myeloma-therapy-deep-sustained-treatment-response-and-good-clinical-outcomes
#12
REVIEW
O Landgren, K Iskander
In the USA at the beginning of this century, the average overall survival in patients with multiple myeloma was about 3 years. Around that time, three drugs (bortezomib, lenalidomide and thalidomide) were introduced for the treatment of multiple myeloma and, in 2012, carfilzomib received accelerated approval by the US Food and Drug Administration (FDA). Driven by access to better drugs, median overall survival in younger patients (aged <50 years) was >10 years by 2014. The FDA approved 14 new drugs for the treatment of cancer in 2015; four of these were approved for the treatment of myeloma (panobinostat, daratumumab, elotuzumab and ixazomib)...
February 16, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28203342/optimizing-current-and-emerging-therapies-in-multiple-myeloma-a-guide-for-the-hematologist
#13
REVIEW
Shahzad Raza, Rachael A Safyan, Evan Rosenbaum, Alex S Bowman, Suzanne Lentzsch
Multiple myeloma (MM) is the second most common hematologic malignancy. The diagnosis of MM requires ⩾10% clonal plasma cells in the bone marrow or biopsy-proven plasmacytoma, plus evidence of end-organ damage (hypercalcemia, renal failure, anemia, and lytic bone lesions). The definition of MM has recently been expanded to include a ⩾60% clonal plasma cell burden in the bone marrow, serum involved/uninvolved light chain ratio of ⩾100, or more than one focal lesion on magnetic resonance imaging ⩾5 mm in the absence of end-organ damage...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28151709/progress-and-paradigms-in-multiple-myeloma
#14
EDITORIAL
Kenneth C Anderson
Remarkable progress has been achieved in multiple myeloma, and patient median survival has been extended 3- to 4-fold. Specifically, there have been 18 newly approved treatments for multiple myeloma in the past 12 years, including seven in 2015, and the treatment paradigm and patient outcome have been transformed. The definition of patients benefitting from these therapies has been broadened. Response criteria now include minimal residual disease (MRD), assessed in bone marrow by multicolor flow cytometry or sequencing, and by imaging for extramedullary disease...
November 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28110581/triplet-combinations-in-relapsed-refractory-myeloma-update-on-recent-phase-3-trials
#15
REVIEW
Jean-Samuel Boudreault, Cyrille Touzeau, Philippe Moreau
Multiple myeloma (MM) is a rare hematologic disease of antibody-secreting plasma cells. Our understanding of the pathogenesis of this malignancy has improved greatly, and at the same time, we have access to new and more effective treatments options. Over the last 5 years, a spectrum of novel therapies with different mechanisms of action, including third-generation immunomodulatory drugs (pomalidomide), second generation proteasome inhibitors (carfilzomib and ixazomib), a histone deacetylase inhibitor (panobinostat) and monoclonal antibodies (mAbs) (elotuzumab and daratumumab) has transformed our approach to the treatment of patients with relapsed/refractory MM (RRMM)...
March 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28007655/ixazomib-suppresses-human-dendritic-cell-and-modulates-murine-graft-versus-host-disease-in-a-schedule-dependent-fashion
#16
Ahmad Samer Al-Homsi, Austin Goodyke, Kelli Cole, Marlee Muilenburg, Michael McLane, Sarah Abdel-Mageed, Yuxin Feng
There is an abiding need for innovative approaches to the prevention of graft-versus-host disease (GvHD) following allogeneic hematopoietic stem cell transplantation (HSCT). Interest in prevention of GvHD by dendritic cell (DC) suppression has re-emerged since the introduction of proteasome inhibitors into clinical practice. Ixazomib is an orally bioavailable proteasome inhibitor with a rapid proteasome dissociation rate. We studied the effects of ixazomib on human DC maturation, viability, and cytokine production in vitro...
December 19, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/28000099/phase-1-study-of-ixazomib-alone-or-combined-with-lenalidomide-dexamethasone-in-japanese-patients-with-relapsed-refractory-multiple-myeloma
#17
Kenshi Suzuki, Hiroshi Handa, Takaaki Chou, Kenichi Ishizawa, Takatoshi Takubo, Yoichi Kase
We report the first clinical investigation conducted in Japan to confirm the safety, tolerability, and pharmacokinetics of ixazomib alone and combined with lenalidomide-dexamethasone (Rd) in Japanese patients with relapsed/refractory multiple myeloma. Adult patients with measurable disease and ≥2 prior lines of therapy received oral ixazomib 4.0 mg on days 1, 8, 15 alone or combined with lenalidomide 25 mg on days 1-21 and dexamethasone 40 mg on days 1, 8, 15, 22 in 28-day cycles. Fourteen patients who had received a median of seven prior therapies were enrolled (seven per cohort)...
April 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/27913521/sequencing-of-nontransplant-treatments-in-multiple-myeloma-patients-with-active-disease
#18
REVIEW
Andrew J Yee, Noopur S Raje
The approval of several different classes of drugs in recent years has resulted in a dramatic expansion of treatment options for multiple myeloma patients, improving both survival and quality of life. Lenalidomide and bortezomib are now core components of treatment both at time of diagnosis and at relapse. Next-generation immunomodulatory drugs, like pomalidomide, and newer proteasome inhibitors like carfilzomib and ixazomib are available for use at relapse. Drugs with novel mechanisms of action such as the histone deacetylase inhibitor panobinostat and the monoclonal antibodies targeting SLAMF7 (elotuzumab) and CD38 (daratumumab) are significant steps forward...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27894203/management-of-adverse-events-induced-by-next-generation-immunomodulatory-drug-and-proteasome-inhibitors-in-multiple-myeloma
#19
REVIEW
Marco Salvini, Francesca Bonello, Mario Boccadoro, Alessandra Larocca
In the last decade the introduction of novel agents has strongly improved multiple myeloma prognosis by doubling median overall survival. Unfortunately disease relapse is very common and patients may become refractory to previous drugs. Therefore, new therapeutic strategies are urgently needed. Areas covered: We have reviewed the available data on next generation novel agents, particularly immunomodulatory drug pomalidomide and proteasome inhibitors carfilzomib and ixazomib, the latter being the first-in-class orally available...
January 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/27888768/multiple-myeloma-treatment-at-relapse-after-autologous-stem-cell-transplantation-a-practical-analysis
#20
REVIEW
F Malard, J L Harousseau, M Mohty
Over the past decade, significant advances have been made in the field of multiple myeloma. Introduction of the so-called novel agents, proteasome inhibitors (PI) and immunomodulatory drugs (IMiD), and improved supportive care have resulted in significantly better outcome. Standard first line treatment in fit patients include PI and IMiD based induction, high dose melphalan with autologous hematopoietic stem cell transplantation (ASCT) and consolidation/maintenance. However, despite these progresses MM remains incurable for the majority of patients and most patients will relapse...
January 2017: Cancer Treatment Reviews
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