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relapsed multiple myeloma

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https://www.readbyqxmd.com/read/28643017/safety-and-efficacy-of-daratumumab-in-japanese-patients-with-relapsed-or-refractory-multiple-myeloma-a-multicenter-phase-1-dose-escalation-study
#1
Shinsuke Iida, Kenshi Suzuki, Shigeru Kusumoto, Masaki Ri, Nobuhiro Tsukada, Yu Abe, Masayuki Aoki, Mitsuo Inagaki
Safety, efficacy, and pharmacokinetics (PK) of daratumumab as a monotherapy were investigated in Japanese patients with relapsed/refractory multiple myeloma (MM). This multicenter, dose-escalation study included patients (age ≥20 years) with ≥2 prior therapies. Daratumumab was administered intravenously: 8 mg/kg (n = 4) and 16 mg/kg (n = 5). The primary endpoint was safety. Secondary endpoints included objective response, overall response rate (ORR), progression-free survival (PFS), PK, and immunogenicity...
June 22, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28642620/pomalidomide-bortezomib-and-low-dose-dexamethasone-in-lenalidomide-refractory-and-proteasome-inhibitor-exposed-myeloma
#2
P G Richardson, C C Hofmeister, N S Raje, D S Siegel, S Lonial, J Laubach, Y A Efebera, D H Vesole, A K Nooka, J Rosenblatt, D Doss, M H Zaki, A Bensmaine, J Herring, Y Li, L Watkins, M S Chen, K C Anderson
This phase 1 dose-escalation study evaluated pomalidomide, bortezomib (subcutaneous (SC) or intravenous (IV)) and low-dose dexamethasone (LoDEX) in lenalidomide-refractory and proteasome inhibitor-exposed relapsed or relapsed and refractory multiple myeloma (RRMM). In 21-day cycles, patients received pomalidomide (1-4 mg days 1-14), bortezomib (1-1.3 mg/m(2) days 1, 4, 8 and 11 for cycles 1-8; days 1 and 8 for cycle ⩾9) and LoDEX. Primary endpoint was to determine the maximum tolerated dose (MTD). Thirty-four patients enrolled: 12 during escalation, 10 in the MTD IV bortezomib cohort and 12 in the MTD SC bortezomib cohort...
June 2, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28637662/daratumumab-plus-pomalidomide-and-dexamethasone-in-relapsed-and-or-refractory-multiple-myeloma
#3
Ajai Chari, Attaya Suvannasankha, Joseph W Fay, Bertrand Arnulf, Jonathan L Kaufman, Jainulabdeen J Ifthikharuddin, Brendan M Weiss, Amrita Krishnan, Suzanne Lentzsch, Raymond Comenzo, Jianping Wang, Kerri Nottage, Christopher Chiu, Nushmia Z Khokhar, Tahamtan Ahmadi, Sagar Lonial
Daratumumab plus pomalidomide/dexamethasone (pom-dex) was evaluated in patients with relapsed/refractory multiple myeloma with ≥2 prior lines of therapy, and who were refractory to their last treatment. Patients received daratumumab 16 mg/kg at the recommended dosing schedule, pomalidomide 4 mg daily for 21 days of each 28-day cycle, and dexamethasone 40 mg weekly. Safety was the primary endpoint. Overall response rate (ORR) and minimal residual disease (MRD) by next-generation sequencing were secondary endpoints...
June 21, 2017: Blood
https://www.readbyqxmd.com/read/28636627/plasma-cell-neoplasia-after-kidney-transplantation-french-cohort-series-and-review-of-the-literature
#4
Raphaël Kormann, Hélène François, Thibault Moles, Jacques Dantal, Nassim Kamar, Karine Moreau, Thomas Bachelet, Anne-Elisabeth Heng, Antoine Garstka, Charlotte Colosio, Didier Ducloux, Johnny Sayegh, Benjamin Savenkoff, Denis Viglietti, Rebecca Sberro, Eric Rondeau, Julie Peltier
Although post-transplant lymphoproliferative disorder (PTLD) is the second most common type of cancer in kidney transplantation (KT), plasma cell neoplasia (PCN) occurs only rarely after KT, and little is known about its characteristics and evolution. We included twenty-two cases of post-transplant PCN occurring between 1991 and 2013. These included 12 symptomatic multiple myeloma, eight indolent myeloma and two plasmacytomas. The median age at diagnosis was 56.5 years and the median onset after transplantation was 66...
2017: PloS One
https://www.readbyqxmd.com/read/28633036/recent-advances-in-understanding-multiple-myeloma
#5
REVIEW
Parameswaran Hari
There have been major recent advancements in the understanding and management of multiple myeloma which in turn has led to unprecedented survival outcomes for patients. Diagnostic and response criteria have been recently revised. Our understanding of clonal progression, evolution, and clonal tides will inform therapeutic choices and appropriate treatment for patients. Response rates to initial induction with modern triplet therapies containing proteasome inhibitors and immunomodulators have made this approach the global standard for initial treatment...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28623912/role-of-epigenetics-microrna-axis-in-drug-resistance-of-multiple-myeloma
#6
REVIEW
Nasrin Rastgoo, Jahangir Abdi, Jian Hou, Hong Chang
Despite administration of novel therapies, multiple myeloma (MM) remains incurable with resistance to drugs leading to relapse in most patients. Thus, it is critical to understand the detailed mechanisms underlying the drug resistance of MM and develop more effective therapeutic strategies. Genetic abnormalities are well known to play a central role in MM pathogenesis and therapy resistance; however, epigenetic aberrations mainly affecting the patterns of DNA methylation/histone modifications of genes (especially tumor suppressors) and miRNAs have also been shown to be involved...
June 17, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28620163/natural-history-of-relapsed-myeloma-refractory-to-immunomodulatory-drugs-and-proteasome-inhibitors-a-multicenter-imwg-study
#7
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/28615223/daratumumab-yields-rapid-and-deep-hematologic-responses-in-patients-with-heavily-pretreated-al-amyloidosis
#8
Gregory P Kaufman, Stanley L Schrier, Richard A Lafayette, Sally Arai, Ronald M Witteles, Michaela Liedtke
The majority of patients with immunoglobulin light chain amyloidosis (AL) fail to achieve a complete response (CR) to standard light chain suppressive chemotherapy, and almost all patients eventually experience hematologic relapse and progression of organ involvement; additional well tolerated treatment options are therefore needed. We present our retrospective experience of 25 consecutive previously treated AL patients who received daratumumab, a CD38-directed monoclonal antibody approved for the treatment of multiple myeloma...
June 14, 2017: Blood
https://www.readbyqxmd.com/read/28612451/transplantation-related-toxicity-and-mortality-in-older-autologous-hematopoietic-cell-transplantation-recipients
#9
Hewan Belete, Linda J Burns, Ryan Shanley, Manju Nayar, Brian McClune, Aleksandr Lazaryan, Veronika Bachanova, Nelli Bejanyan, Celalettin Ustun, Claudio Brunstein, Daniel J Weisdorf, Mukta Arora
With advances in supportive care, autologous hematopoietic cell transplant (AHCT) is increasingly being performed for patients older than 60 years. We analyzed patients receiving an AHCT for multiple myeloma or lymphoma in a contemporary cohort (2010-2012), with consistent treatment and supportive care and compared outcomes [CTCAE grade 3-5 toxicities, non-relapse mortality (NRM) and overall-survival (OS)] of younger (40-59 years, n=77) versus older (≥ 60 years, n=67) recipients. The proportion of patients with neutropenic infections was higher in the older group (64% vs...
June 13, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28610537/overcoming-multiple-myeloma-drug-resistance-in-the-era-of-cancer-omics
#10
Matthew Ho Zhi Guang, Amanda McCann, Giada Bianchi, Li Zhang, Paul Dowling, Despina Bazou, Peter O'Gorman, Kenneth C Anderson
Multiple myeloma (MM) is among the most compelling examples of cancer in which research has markedly improved the length and quality of lives of those afflicted. Research efforts have led to 18 newly approved treatments over the last 12 years, including seven in 2015. However, despite significant improvement in overall survival, MM remains incurable as most patients inevitably, yet unpredictably, develop refractory disease. Recent advances in high-throughput 'omics' techniques afford us an unprecedented opportunity to (1) understand drug resistance at the genomic, transcriptomic, and proteomic level; (2) discover novel diagnostic, prognostic, and therapeutic biomarkers; (3) develop novel therapeutic targets and rational drug combinations; and (4) optimize risk-adapted strategies to circumvent drug resistance, thus bringing us closer to a cure for MM...
June 13, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28604269/elotuzumab-as-a-novel-anti-myeloma-immunotherapy
#11
Sabarinath Venniyil Radhakrishnan, Neelam Bhardwaj, Mary Steinbach, Janet Weidner, Tim Luetkens, Djordje Atanackovic
Treatment of multiple myeloma has undergone significant change in the last decade with the introduction of new immunomodulatory agents, proteasome inhibitors, and immunotherapeutic approaches. Elotuzumab is a humanized monoclonal antibody targeting CS1, which is a member of the SLAM (Signaling Lymphocyte Activation Molecule) family of proteins, expressed on the surface of myeloma plasma cells. Here we review the preclinical investigations that led to the development of elotuzumab and the clinical studies that resulted in its approval for the treatment of relapsed/refractory multiple myeloma...
June 12, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28604120/current-and-developing-synthetic-pharmacotherapy-for-treating-relapsed-refractory-multiple-myeloma
#12
Klaus Podar, Martin Pecherstorfer
The introduction of novel agents has significantly improved multiple myeloma (MM) patient outcome during the last two decades. MM received the most drug approvals for any one malignancy during this time period, both in the United States as well as in Europe. Areas covered: Proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies are prototype drug classes, which target both specific MM cell functions, as well as the tumor supportive bone marrow microenvironment, and represent current cornerstones of MM therapy...
June 12, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28601492/new-agents-in-multiple-myeloma-an%C3%A2-examination-of-safety-profiles
#13
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
#14
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/28596474/lenalidomide-increases-human-dendritic-cell-maturation-in-multiple-myeloma-patients-targeting-monocyte-differentiation-and-modulating-mesenchymal-stromal-cell-inhibitory-properties
#15
Federica Costa, Rosanna Vescovini, Marina Bolzoni, Valentina Marchica, Paola Storti, Denise Toscani, Fabrizio Accardi, Laura Notarfranchi, Benedetta Dalla Palma, Cristina Manferdini, Sabrina Manni, Giannalisa Todaro, Gina Lisignoli, Francesco Piazza, Franco Aversa, Nicola Giuliani
The use of Lenalidomide (LEN), to reverse tumor-mediated immune suppression and amplify multiple myeloma-specific immunity is currently being explored. Particularly, LEN effects on dendritic cells (DCs) are still unclear. In this study, we investigated the potential effect of LEN on DC differentiation and activity. DCs were differentiated either from CD14+ cells obtained from patients with multiple myeloma or from a human monocytic cell line.LEN, at the concentration range reached in vivo, significantly increased the median intensity expression of HLA-DR, CD86 and CD209 by DCs derived from both bone marrow and peripheral myeloma monocytes and enhanced the production of Interleukin-8, C-C motif chemokine ligand (CCL) 2, CCL5 and tumor necrosis factor-α...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28594589/mek-inhibitors-in-oncology-a-patent-review-2015-present
#16
Debarshi Kar Mahapatra, Vivek Asati, Sanjay Kumar Bharti
The RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathways have been identified as promising therapeutic targets for cancer therapy. Over-activation of these pathways and their components including gene mutations has been considered as one of the major causes of melanoma. Mitogen-activated protein kinase (MEK) is a downstream kinase of RAS pathway found in two different forms MEK1/2. The MEK inhibitors in combination with other kinase/mutant gene inhibitors have shown promising results in patients with metastatic melanoma...
June 19, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28592756/cea-producing-multiple-myeloma-with-meningeal-invasion-during-relapse
#17
Mayumi Hatsuse, Shin-Ichi Fuchida, Akira Okano, Satoshi Murakami, Chihiro Shimazaki
Here we describe the case of a 62-year-old woman diagnosed with multiple myeloma (IgA-κ type) who had a high serum CEA level of 27.7 ng/ml. Upper and lower gastrointestinal endoscopy and PET/CT scan showed no abnormality. After two courses of VAD therapy, the serum CEA level decreased to 5.7 ng/ml, with a decrease in the IgA level, suggesting the diagnosis of CEA-producing myeloma. After 4 years and 1 month, she had a relapse with an increase in the LDH level and myeloma cells in the blood, followed by cognitive loss and convulsion...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28588060/sending-car-t-cells-after-multiple-myeloma
#18
(no author information available yet)
Preliminary results from an ongoing phase I clinical trial in China suggest that chimeric antigen receptor T cells engineered to home in on a protein called BCMA may be a potent therapeutic option for multiple myeloma. The therapy was well tolerated and induced complete, durable responses in patients with relapsed/refractory disease.
June 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28584253/prediction-of-outcome-in-newly-diagnosed-myeloma-a-meta-analysis-of-the-molecular-profiles-of-1-905-trial-patients
#19
V Shah, A L Sherborne, B A Walker, D C Johnson, E M Boyle, S Ellis, D B Begum, P Z Proszek, J R Jones, C Pawlyn, S Savola, M W Jenner, M T Drayson, R G Owen, R S Houlston, D A Cairns, W M Gregory, G Cook, F E Davies, G H Jackson, G J Morgan, M F Kaiser
Robust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1...
June 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28583668/-pomalidomide-for-multiple-myeloma
#20
Aurore Dougé, Richard Lemal, Carine Chaleteix
Pomalidomide is a second-generation immunomodulatory drug (IMID). Its efficiency overtakes its predecessors' (thalidomide, lenalidomide), with less toxicity. It is indicated in the treatment of refractory or relapsed multiple myeloma, associated to dexamethasone. It is available in France since 2013, following the results of different studies.
June 2, 2017: Bulletin du Cancer
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