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https://www.readbyqxmd.com/read/27913521/sequencing-of-nontransplant-treatments-in-multiple-myeloma-patients-with-active-disease
#1
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/27913520/myeloma-management-of-the-newly-diagnosed-high-risk-patient
#2
Angela Dispenzieri
Although there have been many definitions for high-risk (HR) myeloma, most recent consensus for classifying risk in patients with newly diagnosed multiple myeloma (NMM) comes from the International Myeloma Working Group. This recently published revised International Staging System includes del(17p) or t(4;14) by fluorescence in situ hybridization, β-2 microglobulin, albumin, and lactate dehydrogenase. These elements should be captured in all NMM patients. The optimal treatments for HR myeloma have not been fully worked out; therefore, these patients should be considered for clinical trials...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27910963/daratumumab-monoclonal-antibody-therapy-to-treat-multiple-myeloma
#3
C Xia, M Ribeiro, S Scott, S Lonial
Daratumumab (Darzalex[TM]) is a human monoclonal antibody (MAb) that targets CD38; a surface protein highly expressed across multiple myeloma (MM) cells. Preclinical studies have shown daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis upon secondary crosslinking and immunomodulatory effects via a decrease in immune suppressive cells. Daratumumab has a favorable toxicity profile and encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) and stem cell transplant have already failed...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27904139/interphase-fluorescence-in-situ-hybridization-ifish-in-untreated-al-amyloidosis-has-an-independent-prognostic-impact-by-abnormality-type-and-treatment-category
#4
E Muchtar, A Dispenzieri, S K Kumar, R P Ketterling, D Dingli, M Q Lacy, F K Buadi, S R Hayman, P Kapoor, N Leung, R Chakraborty, W Gonsalves, R Warsame, T V Kourelis, S Russell, J A Lust, Y Lin, R S Go, S Zeldenrust, R A Kyle, S V Rajkumar, M A Gertz
The significance of interphase fluorescence in-situ hybridization (iFISH) by regimen type was assessed in 692 AL amyloidosis patients with iFISH at diagnosis. First line treatment was categorized as stem cell transplant and three non-transplant regimens. The most common abnormality was t(11;14) (49% of patients) followed by monosomy 13/del(13q) (36%) and trisomies (26%). A lower rate of very good partial response (VGPR) or better was observed in patients with t(11;14) treated with bortezomib-based (52 vs 77%; P=0...
December 1, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27893836/prognostic-value-of-serum-free-light-chains-measurements-in-multiple-myeloma-patients
#5
José Luis García de Veas Silva, Carmen Bermudo Guitarte, Paloma Menéndez Valladares, Johanna Carolina Rojas Noboa, Krysta Kestler, Rafael Duro Millán
BACKGROUND: The outcome for patients with Multiple Myeloma (MM) is highly variable, therefore, the existence of robust and easy to determine prognostic markers is extremely important for an efficient management of these patients. Presently, there is a debate about the role of the serum free light chains (sFLC) in the prognosis of MM patients both at diagnosis and after treatment. The aim of this study is to evaluate in a cohort of newly diagnosed MM patients from the Southern area of Spain, the prognostic value of sFLC both at baseline and after treatment...
2016: PloS One
https://www.readbyqxmd.com/read/27864218/second-primary-malignancies-in-multiple-myeloma-an-overview-and-imwg-consensus
#6
REVIEW
P Musto, K C Anderson, M Attal, P G Richardson, A Badros, J Hou, R Comenzo, J Du, B G M Durie, J San Miguel, H Einsele, W M Chen, L Garderet, G Pietrantuono, J Hillengass, R A Kyle, P Moreau, J J Lahuerta, O Landgren, H Ludwig, A Larocca, A Mahindra, M Cavo, A Mazumder, P L McCarthy, A Nouel, S V Rajkumar, A Reiman, E R Serra, O Sezer, E Terpos, I Turesson, S Usmani, B M Weiss, A Palumbo
BACKGROUND: Therapeutic advancements following the introduction of autologous stem cell transplantation and 'novel' agents have significantly improved clinical outcomes for patients with multiple myeloma (MM). Increased life expectancy, however, has led to renewed concerns about the long-term risk of second primary malignancies (SPMs). This review outlines the most up-to-date knowledge of possible host-, disease-, and treatment-related risk factors for the development of SPMs in patients with MM, and provides practical recommendations to assist physicians...
November 17, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27864161/maintenance-versus-induction-therapy-choice-on-outcomes-after-autologous-transplantation-for-multiple-myeloma
#7
Robert F Cornell, Anita D'Souza, Adetola A Kassim, Luciano J Costa, Racquel D Innis-Shelton, Mei-Jie Zhang, Jiaxing Huang, Muneer Abidi, Jack Aiello, Gorgun Akpek, Asad Bashey, Qaiser Bashir, Jan Cerny, Raymond Comenzo, Miguel Angel Diaz, César Freytes, Robert Peter Gale, Siddhartha Ganguly, Mehdi Hamadani, Shahrukh Hashmi, Leona Holmberg, Nasheed Hossain, Rammurti T Kamble, Mohamed Kharfan-Dabaja, Tamila Kindwall-Keller, Robert Kyle, Shaji Kumar, Hillard Lazarus, Cindy Lee, Angelo Maiolino, David I Marks, Kenneth Meehan, Joe Mikhael, Rajneesh Nath, Taiga Nishihori, Richard F Olsson, Muthalagu Ramanathan, Ayman Saad, Sachiko Seo, Saad Usmani, David Vesole, Ravi Vij, Dan Vogl, Baldeep M Wirk, Jean Yared, Amrita Krishnan, Tomer Mark, Yago Nieto, Parameswaran Hari
Bortezomib (V), lenalidomide (R), cyclophosphamide (C) and dexamethasone (D) are components of the most commonly used modern doublet (RD, VD) or triplet (VRD, CVD) initial induction regimens prior to autologous hematopoietic cell transplantation (AHCT) for multiple myeloma (MM) in the US. In this study we evaluated 693 patients receiving "upfront" AHCT after initial induction therapy with modern doublet or triplet regimens using data reported to the Center for International Blood and Marrow Transplant Research from 2008-2013...
November 15, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27863874/successful-autologous-haematopoietic-stem-cell-transplantation-for-refractory-myasthenia-gravis-a-case-report
#8
Irene Håkansson, Anna Sandstedt, Fredrik Lundin, Håkan Askmark, Ritva Pirskanen, Kristina Carlson, Fredrik Piehl, Hans Hägglund
Myasthenia gravis (MG) is an autoimmune disease, with immune reactivity against the post-synaptic endplate of the neuromuscular junction. Apart from symptomatic treatment with choline esterase blockers, many patients also require immunomodulatory treatment. Despite existing treatment options, some patients are treatment refractory. We describe a patient with severe MG refractory to corticosteroids, four oral immunosuppressants, cyclophosphamide, rituximab and bortezomib who was treated with autologous haematopoietic stem cell transplantation...
September 28, 2016: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/27859769/association-between-complete-response-and-outcomes-in-transplant-eligible-myeloma-patients-in-the-era-of-novel-agents
#9
Helgi van de Velde, Anil Londhe, Ataman Ozlem, Helen L Johns, Stephen Hill, Emma Landers, Jesse A Berlin
OBJECTIVES: Achieving complete response (CR) has been linked to improved progression-free (PFS) and overall (OS) survival in myeloma. A meta-analysis was conducted to investigate whether this holds true in the era of novel agents (bortezomib, lenalidomide, thalidomide). METHODS: 24 studies in newly diagnosed patients undergoing autologous stem cell transplantation (ASCT) that reported associations between responses and long-term outcomes (PFS/OS rates post-ASCT by response, or hazard ratios with 95% confidence intervals from Cox models) were identified and analyzed...
November 16, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27856369/outcomes-of-maintenance-therapy-with-bortezomib-post-autologous-stem-cell-transplantation-for-patients-with-multiple-myeloma
#10
Dharshan Sivaraj, Michael M Green, Zhiguo Li, Anthony D Sung, Stefanie Sarantopoulos, Yubin Kang, Gwynn D Long, Mitchell E Horwitz, Richard D Lopez, Keith M Sullivan, David A Rizzieri, Nelson J Chao, Cristina Gasparetto
Comprehensive recommendations for maintenance therapy post-autologous stem cell transplantation (ASCT) for patients with multiple myeloma (MM) have yet to be defined. Bortezomib has been utilized as maintenance therapy after ASCT, but data attesting to the safety and efficacy of this agent compared to lenalidomide in the post-ASCT setting are limited. Therefore we retrospectively analyzed the outcomes of 102 MM patients who received maintenance therapy with bortezomib post-ASCT at Duke University's Adult Bone Marrow Transplant Clinic (ABMT) between 2005 and 2015...
November 14, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27843120/bortezomib-thalidomide-dexamethasone-and-panobinostat-for-patients-with-relapsed-multiple-myeloma-muk-six-a-multicentre-open-label-phase-1-2-trial
#11
Rakesh Popat, Sarah R Brown, Louise Flanagan, Andrew Hall, Walter Gregory, Bhuvan Kishore, Matthew Streetly, Heather Oakervee, Kwee Yong, Gordon Cook, Eric Low, Jamie Cavenagh
BACKGROUND: Panobinostat (a pan histone deacetylase inhibitor) is approved in combination with bortezomib and dexamethasone for patients with relapsed multiple myeloma who have received two or more previous lines of therapy. We aimed to improve the safety of this combination and investigate efficacy by incorporating low-dose thalidomide, using sub-cutaneous weekly bortezomib, and determining the maximum tolerated dose of panobinostat in this regimen. METHODS: We did a phase 1/2, multicentre, open-label trial (MUK six) at four hospitals in the UK, enrolling patients with relapsed, or relapsed and refractory, multiple myeloma aged at least 18 years, with an Eastern Cooperative Oncology Group performance status of 2 or less who had previously received 1-4 lines of therapy...
November 11, 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27832515/bortezomib-dexamethasone-versus-high-dose-melphalan-for-japanese-patients-with-systemic-light-chain-al-amyloidosis-a-retrospective-single-center-study
#12
Nagaaki Katoh, Akihiro Ueno, Takuhiro Yoshida, Ko-Ichi Tazawa, Yasuhiro Shimojima, Takahisa Gono, Yoshiki Sekijima, Masayuki Matsuda, Shu-Ichi Ikeda
Bortezomib-dexamethasone (BD) and high-dose melphalan (HDM) are effective for systemic light-chain (AL) amyloidosis, but have not been compared in detail. We retrospectively investigated patients treated with BD or HDM at our center between September 2001 and June 2016. Among 234 patients, 20 were treated with BD and 30 received HDM. With the exception of age, transplant eligibility, and previous history of other chemotherapy, there were no significant differences in most background parameters between the two groups...
November 10, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27819033/successful-kidney-transplantation-after-stepwise-desensitization-using-rituximab-and-bortezomib-in-a-highly-hla-sensitized-and-abo-incompatible-high-titer-patient
#13
Masashi Inui, Tomonori Miyazato, Miyuki Furusawa, Masayoshi Okumi, Kazuya Omoto, Hideki Ishida, Kazunari Tanabe
No abstract text is available yet for this article.
August 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27815049/therapeutic-effects-of-a-nedd8-activating-enzyme-inhibitor-pevonedistat-on-sclerodermatous-graft-versus-host-disease-in-mice
#14
Chien-Chun Steven Pai, Lam T Khuat, Mingyi Chen, William J Murphy, Mehrdad Abedi
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the ultimate treatment for highly malignant hematologic disease; however, the major complication-graft-versus-host disease (GVHD)-still hinders its clinical application. In addition, chronic GVHD remains the major cause of long-term morbidity and mortality after allo-HSCT. Previously we showed that bortezomib, a proteasome inhibitor, can ameliorate the sclerodermatous GVHD response while maintaining graft-versus-tumor (GVT) effects. Here we report that pevonedistat (MLN4924), an inhibitor of the Nedd8-activating enzyme, which functions upstream of the proteasome in the ubiquitin-proteasome pathway, can also show similar protective effects...
November 1, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27810902/adverse-metaphase-cytogenetics-can-be-overcome-by-adding-bortezomib-and-thalidomide-to-fractionated-melphalan-transplants
#15
Yogesh Jethava, Alan Mitchell, Joshua Epstein, Maurizio Zangari, Shmuel Yaccoby, Erming Tian, Sarah Waheed, Rashid Khan, Xenofon Papanikolaou, Monica Grazziutti, Michele Cottler-Fox, Nathan Petty, Douglas Steward, Susan Panozzo, Clyde Bailey, Antje Hoering, John Crowley, Jeffrey Sawyer, Gareth Morgan, Bart Barlogie, Frits van Rhee
PURPOSE: To determine whether a reduction in the intensity of Total Therapy (TT) reduces toxicity and maintains efficacy. EXPERIMENTAL DESIGN: 289 patients with gene expression profiling (GEP70)-defined low-risk multiple myeloma (LRMM) were randomized between a standard arm (TT4-S) and a light arm (TT4-L). TT4-L employed 1 instead of 2 inductions and consolidations. To compensate for potential loss of efficacy of TT4-L, bortezomib and thalidomide were added to fractionated melphalan 50mg/m2/d x 4...
November 3, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27795517/treatment-strategy-for-transplant-ineligible-patients-with-newly-diagnosed-multiple-myeloma
#16
Hideto Tamura
The current therapeutic strategy for multiple myeloma has improved dramatically due to the use of novel agents. In newly diagnosed transplant-ineligible myeloma patients, the standard therapy until the 1990s had long been melphalan and prednisolone (MP), but the recent recommendation is the proteasome inhibitor bortezomib plus MP (MPB), the immunomodulatory drug thalidomide plus MP (MPT), and the thalidomide derivative lenalidomide (LEN)-based regimens such as LEN plus low-dose dexamethasone (Ld) and LEN plus MP (MPL)...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27795516/treatment-strategy-in-untreated-transplant-eligible-multiple-myeloma-patients
#17
Kazutaka Sunami
Autologous stem cell transplantation (ASCT) is known to be superior to conventional chemotherapies and has been established as a standard of care for young patients with multiple myeloma. In the first decade of this century, novel agents such as thalidomide, bortezomib, and lenalidomide became clinically available, and several clinical trials using these drugs as induction therapies, conditioning regimens, and post-transplant consolidation and maintenance therapies have been reported, leading to increasing improvement in treatment results as compared to conventional therapies...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27789676/evaluation-of-the-revised-international-staging-system-r-iss-in-an-independent-cohort-of-unselected-patients-with-multiple-myeloma
#18
Efstathios Kastritis, Evangelos Terpos, Maria Roussou, Maria Gavriatopoulou, Magdalini Migkou, Evangelos Eleutherakis-Papaiakovou, Despoina Fotiou, Dimitrios Ziogas, Ioannis Panagiotidis, Eftychia Kafantari, Stavroula Giannouli, Athanasios Zomas, Konstantinos Konstantopoulos, Meletios A Dimopoulos
The revised International Staging System (R-ISS) was recently introduced in order to improve risk stratification over the widely used ISS. R-ISS incorporates, in addition to ISS, the presence of chromosomal abnormalities detected by iFISH (t(4;14), t(14;16) and del17p) and elevated serum lactate dehydrogenase. R-ISS formulation was based on a large dataset of selected patients who had participated in clinical trials and has not been validated in an independent cohort of unselected patients. Thus, we evaluated R-ISS in 475 consecutive, unselected patients, treated in a single center...
October 27, 2016: Haematologica
https://www.readbyqxmd.com/read/27762125/bortezomib-based-chemotherapy-for-light-chain-deposition-disease
#19
Vignesh Kandakumar, Vishnu Nagalapuram, Sujaya Menon
Light chain deposition disease (LCDD) is a rare systemic disorder in which monoclonal light chains are abnormally secreted due to clonal proliferation of plasma cells and get deposited in various organs; the kidneys being the common one to be affected leading to renal failure. Advocated therapeutic options include chemotherapy with alkylating agents and steroids, High-Dose Melphalan (HDM) with Autologous Stem Cell Transplantation. Recently, Bortezomib has proven to be a novel therapeutic option in these patients when combined with dexamethasone...
August 2016: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/27738789/outcomes-with-two-different-schedules-of-bortezomib-melphalan-and-prednisone-vmp-for-previously-untreated-multiple-myeloma-matched-pair-analysis-using-long-term-follow-up-data-from-the-phase-3-vista-and-pethema-gem05-trials
#20
Maria-Victoria Mateos, Albert Oriol, Joaquín Martínez-López, Ana-Isabel Teruel, Enrique Bengoechea, Luis Palomera, Felipe de Arriba, Dixie-Lee Esseltine, Andrew Cakana, Lixia Pei, Helgi van de Velde, Jesus San Miguel
: Bortezomib-melphalan-prednisone (VMP) is a standard-of-care for previously untreated, transplant-ineligible multiple myeloma (MM). Here, we compared outcomes between VMP regimens in the VISTA trial (9-cycle VMP schedule, including 4 cycles of twice weekly bortezomib) and the PETHEMA/GEM05 trial (less intensive 6-cycle VMP schedule with 1 cycle of twice weekly and 5 cycles of weekly bortezomib, then bortezomib-based maintenance). A total of 113 patient pairs matched by propensity score (estimated using logistic regression and incorporating eight exposure/outcome-related parameters) were included in this retrospective analysis...
October 14, 2016: Annals of Hematology
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