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https://www.readbyqxmd.com/read/27910963/daratumumab-monoclonal-antibody-therapy-to-treat-multiple-myeloma
#1
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/27909306/rpl5-on-1p22-1-is-recurrently-deleted-in-multiple-myeloma-and-its-expression-is-linked-to-bortezomib-response
#2
I J F Hofman, M Van Duin, E De Bruyne, L Fancello, G Mulligan, E Geerdens, E Garelli, C Mancini, H Lemmens, M Delforge, P Vandenberghe, I Wlodarska, A Aspesi, L Michaux, K Vanderkerken, P Sonneveld, K De Keersmaecker
Chromosomal region 1p22 is deleted in ⩾20% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5) and ribosomal protein L5 (RPL5). Low mRNA expression of EVI5 and RPL5 was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5 and RPL5, however, 1p22 deletion status is a bad predictor of RPL5 expression in some cases, suggesting that other mechanisms downregulate RPL5 expression...
December 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27909220/role-of-serum-free-light-chain-assay-in-the-detection-of-early-relapse-and-prediction-of-prognosis-after-relapse-in-multiple-myeloma-patients-treated-upfront-with-novel-agents
#3
Paola Tacchetti, Annalisa Pezzi, Elena Zamagni, Lucia Pantani, Serena Rocchi, Beatrice Anna Zannetti, Katia Mancuso, Ilaria Rizzello, Michele Cavo
No abstract text is available yet for this article.
December 1, 2016: Haematologica
https://www.readbyqxmd.com/read/27905203/efficacy-and-toxicity-of-the-combination-chemotherapy-of-thalidomide-alkylating-agent-and-steroid-for-relapsed-refractory-myeloma-patients-a-report-from-the-korean-multiple-myeloma-working-party-kmmwp-retrospective-study
#4
Jihyun Kwon, Chang-Ki Min, Kihyun Kim, Jae-Joon Han, Joon Ho Moon, Hye Jin Kang, Hyeon-Seok Eom, Min Kyoung Kim, Hyo Jung Kim, Dok Hyun Yoon, Jeong-Ok Lee, Won Sik Lee, Jae Hoon Lee, Je-Jung Lee, Yoon-Seok Choi, Sung Hyun Kim, Sung-Soo Yoon
We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35...
December 1, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27904737/a-clinical-update-on-the-role-of-carfilzomib-in-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#5
REVIEW
B Franken, N W C J van de Donk, J C Cloos, S Zweegman, H M Lokhorst
Even though the prognosis of patients with multiple myeloma is continuing to improve, all patients eventually develop relapsed refractory disease. Several novel therapeutics have been developed in the last few years including the second-generation proteasome inhibitor carfilzomib which has been approved for patients with relapsed and refractory multiple myeloma in the United States since 2012. Recently data from several phase III studies have become available showing the promising efficacy of carfilzomib in combination with lenalidomide, which led to the renewed approval of carfilzomib in combination with lenalidomide and dexamethasone for relapsed myeloma in 2015...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27900520/nuclear-medicine-imaging-of-multiple-myeloma-particularly-in-the-relapsed-setting
#6
REVIEW
Esther G M de Waal, Andor W J M Glaudemans, Carolien P Schröder, Edo Vellenga, Riemer H J A Slart
Multiple myeloma (MM) is characterized by a monoclonal plasma cell population in the bone marrow. Lytic lesions occur in up to 90 % of patients. For many years, whole-body X-ray (WBX) was the method of choice for detecting skeleton abnormalities. However, the value of WBX in relapsing disease is limited because lesions persist post-treatment, which restricts the capacity to distinguish between old, inactive skeletal lesions and new, active ones. Therefore, alternative techniques are necessary to visualize disease activity...
November 29, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27899805/circulating-tumour-dna-analysis-demonstrates-spatial-mutational-heterogeneity-that-coincides-with-disease-relapse-in-myeloma
#7
S Mithraprabhu, T Khong, M Ramachandran, A Chow, D Klarica, L Mai, S Walsh, D Broemeling, A Marziali, M Wiggin, J Hocking, A Kalff, B Durie, A Spencer
Mutational characterisation in multiple myeloma (MM) currently relies on bone marrow (BM) biopsy, which fails to capture the putative spatial and genetic heterogeneity of this multi-focal disease. Analysis of plasma (PL)-derived circulating free tumour DNA (ctDNA) as an adjunct to BM biopsy, for mutational characterisation and tracking disease progression, was evaluated. Paired BM MM cell DNA and ctDNA from 33 relapsed [RR] and 15 newly diagnosed [ND] patients were analysed for KRAS, NRAS, BRAF and TP53 mutations using the OnTarget™ Mutation Detection (OMD) platform...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27896689/pharmacokinetics-of-daratumumab-following-intravenous-infusion-in-relapsed-or-refractory-multiple-myeloma-after-prior-proteasome-inhibitor-and-immunomodulatory-drug-treatment
#8
Pamela L Clemens, Xiaoyu Yan, Henk M Lokhorst, Sagar Lonial, Nedjad Losic, Imran Khan, Richard Jansson, Tahamtan Ahmadi, Kristen Lantz, Honghui Zhou, Thomas Puchalski, Xu Steven Xu
Daratumumab is a CD38 monoclonal antibody recently approved for the treatment of multiple myeloma (MM). We report daratumumab pharmacokinetic data from GEN501, a phase I/II dose-escalation (0.005-24 mg/kg) and dose-expansion (8 or 16 mg/kg) study, and SIRIUS, a phase II study (8 or 16 mg/kg), in relapsed or refractory MM. Noncompartmental analysis was conducted to characterize daratumumab pharmacokinetics, and, in both studies, daratumumab exhibited nonlinear pharmacokinetic characteristics. Decreasing daratumumab clearance with increasing dose suggests saturation of target-mediated clearance at higher dose levels, whereas decreasing clearance over time with repeated dosing may be due to tumor burden reductions as CD38-positive cells are eliminated...
November 29, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27894207/when-to-recommend-a-second-autograft-in-patients-with-relapsed-myeloma
#9
Dimitrios C Ziogas, Evangelos Terpos, Meletios A Dimopoulos
In the current evolving landscape of myeloma therapies, no recommended salvage strategy exists for patients with relapsed multiple myeloma (MM) after initial successful autologous stem cell transplantation (ASCT) and therapeutic options extend from conventional chemotherapy and novel agents to second autologous and allogeneic transplants. In this article, we summarize the documented evidence about the utilization of second ASCT in patients with relapsed MM after a primary auto-graft and discuss the correct timing for such a salvage approach, the individual characteristics of patients who will benefit more, as well as the therapeutic role of second ASCT in the modern era of forthcoming anti-myeloma treatments...
November 28, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27894203/management-of-adverse-events-induced-by-next-generation-immunomodulatory-drug-and-proteasome-inhibitors-in-multiple-myeloma
#10
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...
November 29, 2016: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/27893171/salvage-therapy-in-first-relapse-a-retrospective-study-in-a-large-patient-population-with-multiple-myeloma
#11
Massimo Offidani, Laura Corvatta, Sara Bringhen, Silvia Gentili, Rossella Troia, Laura Maracci, Alessandra Larocca, Pietro Leoni, Mario Boccadoro
OBJECTIVE: there is no strong evidence to guide therapeutic approach to multiple myeloma (MM) patients who experience first relapse. The treatment choice can be difficult since currently all patients are exposed to novel agents as thalidomide, bortezomib and lenalidomide. METHODS: in this retrospective analysis we evaluated the best therapeutic sequence, the role of re-treatment and the most beneficial cut-off of first remission in order to choose re-treatment, analyzing 476 patients relapsed after first-line therapy...
November 28, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27888768/multiple-myeloma-treatment-at-relapse-after-autologous-stem-cell-transplantation-a-practical-analysis
#12
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...
November 15, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27884726/deacetylase-inhibitors-as-a-novel-modality-in-the-treatment-of-multiple-myeloma
#13
REVIEW
Paul G Richardson, Philippe Moreau, Jacob P Laubach, Michelle E Maglio, Sagar Lonial, Jesus San-Miguel
Deacetylase enzymes remove acetyl groups from histone and nonhistone proteins. Dysregulation of deacetylase activity is a hallmark of malignancy, including multiple myeloma (MM). Deacetylase inhibitors (DACi) cause epigenetic modification and inhibition of the aggresome pathway, resulting in death of MM cells. Panobinostat, a pan-DACi, has shown significant clinical benefit and is the first DACi approved for the treatment of MM. It is approved for use in combination with bortezomib and dexamethasone for the treatment of patients with relapsed or relapsed and refractory MM who have received ≥2 prior regimens including bortezomib and an immunomodulatory drug...
November 21, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27875670/efficacy-of-carfilzomib-in-the-treatment-of-relapsed-and-or-refractory-multiple-myeloma-a-meta-analysis-of-data-from-clinical-trials
#14
Runzhe Chen, Baoan Chen, Xiaoping Zhang, Chong Gao
OBJECTIVE: Recently, carfilzomib has become a promising therapeutic approach for relapsed and (or) refractory multiple myeloma (RRMM), but no study has summarized the overall effect of carfilzomib in RRMM. To explore the role of carfilzomib, we performed a meta-analysis of all known prospective clinical trials to assess the efficacy of carfilzomib in patients with RRMM. METHODS AND MATERIALS: A systematic review of publications was performed on December 15, 2015...
October 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27870103/role-of-immunotherapy-in-targeting-the-bone-marrow-microenvironment-in-multiple-myeloma-an-evolving-therapeutic-strategy
#15
Clement Chung
Multiple myeloma (referred to henceforth as myeloma) is a B-cell malignancy characterized by unregulated growth of plasma cells in the bone marrow. The treatment paradigm for myeloma underwent significant evolution in the last decade, with an improved understanding of the pathogenesis of the disease as well as the development of therapeutic agents that target not only the tumor cells but also their microenvironment. Despite these therapeutic advances, the prognosis of patients with relapsed or refractory myeloma remains poor...
November 21, 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/27868410/-expression-of-microrna-221-222-in-patients-with-monoclonal-gammopathy-of-undetermined-significance-and-multiple-myeloma
#16
Suwen Yang, Wei Wang, Hong Jin, Yuhong Zhong, Xinyou Xie
Objective: To detect the expression of miR-221/222 in serum and plasma cells in patients with monoclonal gammopathy of undetermined significance(MGUS) and multiple myeloma(MM), and to explore the possibility of miR-221/222 as biomarkers in the diagnosis and prognosis predicting of MGUS and MM. Methods: Bone marrow and serum samples from 14 patients with newly diagnosed MGUS, 81 patients with newly diagnosed or relapsed MM and 10 controls were collected from Sir Run Run Shaw Hospital of Zhejiang University and Tongde Hospital of Zhejiang Province during January 2013 and December 2015...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/27867671/retreatment-with-bendamustine-bortezomib-dexamethasone-in-a-patient-with-relapsed-refractory-multiple-myeloma
#17
Claudio Cerchione, Davide Nappi, Maria Di Perna, Irene Zacheo, Anna Emanuele Pareto, Marco Picardi, Lucio Catalano, Fabrizio Pane
The clinical management of relapsed/refractory multiple myeloma and the correct choice of the most suitable therapy in heavily pretreated and fragile patients are tough clinical issues for clinicians. In advanced phases of disease, the choice of available therapies becomes very poor, and the retreatment with previously adopted and effective therapy, although unpredictable, could be an effective option. In this report, we describe the clinical history of a patient, previously treated with 9 lines of therapy, refractory to bortezomib and IMIDs, for whom the retreatment with bendamustine resulted in a stable disease with good quality of life...
2016: Case Reports in Hematology
https://www.readbyqxmd.com/read/27864161/maintenance-versus-induction-therapy-choice-on-outcomes-after-autologous-transplantation-for-multiple-myeloma
#18
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/27863374/magic-year-for-multiple-myeloma-therapeutics-key-takeaways-from-the-ash-2015-annual-meeting
#19
REVIEW
Kejie Zhang, Aakash Desai, Dongfeng Zeng, Tiejun Gong, Peihua Lu, Michael Wang
Despite the availability of various anticancer agents, Multiple Myeloma (MM) remains incurable in most cases, along with high relapse rate in the patients treated with these agents. The year 2015 saw major advancements in our battle against multiple myeloma. In 2015, the U.S. Food and Drug Administration (FDA) approved three new therapies for multiple myeloma, namely Ixazomib (an oral proteasome inhibitor), Daratumumab and Elotuzumab (monoclonal antibodies against CD38 and SLAMF7 respectively). The purpose of this review is to provide a detailed analysis of these aforementioned breakthrough therapies and two other newer agents, Filanesib (kinesis spindle inhibitor) and selinexor (SINE inhibitor), presented at the 2015 annual meeting of American Society of Hematology (ASH)...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27860411/secondary-primary-malignancies-during-the-lenalidomide-dexamethasone-regimen-in-relapsed-refractory-multiple-myeloma-patients
#20
Rouslan Kotchetkov, Esther Masih-Khan, Chia-Min Chu, Eshetu G Atenafu, Christine Chen, Vishal Kukreti, Suzanne Trudel, Rodger Tiedemann, Donna E Reece
Lenalidomide in combination with dexamethasone (Len-dex) represents a highly effective treatment in relapsed/refractory multiple myeloma (RRMM) patients. However, an increased risk of secondary primary malignancies (SPMs), including myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) has been described in patients receiving lenalidomide. In order to assess the incidence and features of this complication, we reviewed 195 patients with RRMM treated with Len-dex at our institution. The median follow-up time from diagnosis of MM was 73 months (10-234 months) and from initiation of Len-dex was 19 months (1-104 months)...
November 18, 2016: Cancer Medicine
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