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Myeloma treatment

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https://www.readbyqxmd.com/read/29676460/resistance-to-proteasome-inhibitors-and-other-targeted-therapies-in-myeloma
#1
REVIEW
Craig T Wallington-Beddoe, Magdalena Sobieraj-Teague, Bryone J Kuss, Stuart M Pitson
The number of novel therapies for the treatment of myeloma is rapidly increasing, as are the clinical trials evaluating them in combination with other novel and established therapies. Proteasome inhibitors, immunomodulatory agents and monoclonal antibodies are the most well known and studied classes of novel agents targeting myeloma, with histone deacetylase inhibitors, nuclear export inhibitors and several other approaches also being actively investigated. However, in parallel with the development and clinical use of these novel myeloma therapies is the emergence of novel mechanisms of resistance, many of which remain elusive, particularly for more recently developed agents...
April 20, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29675792/maintenance-in-myeloma-patients-achieving-complete-response-after-upfront-therapy-a-pooled-analysis
#2
Chiara Cerrato, Francesco Di Raimondo, Lorenzo De Paoli, Stefano Spada, Francesca Patriarca, Claudia Crippa, Roberto Mina, Tommasina Guglielmelli, Dina Ben-Yehuda, Daniela Oddolo, Chiara Nozzoli, Emanuele Angelucci, Nicola Cascavilla, Rita Rizzi, Stefano Rocco, Luca Baldini, Elena Ponticelli, Magda Marcatti, Clotilde Cangialosi, Tommaso Caravita, Giulia Benevolo, Roberto Ria, Arnon Nagler, Pellegrino Musto, Paola Tacchetti, Paolo Corradini, Massimo Offidani, Antonio Palumbo, Maria Teresa Petrucci, Mario Boccadoro, Francesca Gay
PURPOSE: Maintenance demonstrated to improve survival in newly diagnosed multiple myeloma (NDMM) patients and the achievement of complete response (CR) is a strong predictor of survival. Nevertheless, the role of maintenance according to response after induction/consolidation has not been investigated so far. To evaluate the impact of maintenance according to response, we pooled together and retrospectively analyzed data from 955 NDMM patients enrolled in two trials (GIMEMA-MM-03-05 and RV-MM-PI-209)...
April 19, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29674494/safety-and-efficacy-of-vorinostat-bortezomib-doxorubicin-and-dexamethasone-in-a-phase-i-ii-study-for-relapsed-or-refractory-multiple-myeloma-verumm-study-vorinostat-in-elderly-relapsed-and-unfit-multiple-myeloma
#3
Johannes M Waldschmidt, Alexander Keller, Gabriele Ihorst, Olga Grishina, Stefan Müller, Dagmar Wider, Anna V Frey, Kristina King, Roman Simon, Annette May, Pierfrancesco Tassone, Justus Duyster, Manfred Jung, Noopur Raje, Ralph Wäsch, Monika Engelhardt
This phase I/II trial was conducted to investigate the safety, efficacy, and pharmacodynamics of the pan-HDAC-inhibitor (HDACi) vorinostat combined with bortezomib, doxorubicin, and dexamethasone (VBDD) in patients suffering from relapsed/refractory multiple myeloma (RRMM). In the phase I part of this study, 9/33 patients received dose-escalated vorinostat (100, 200, 300mg), using a 4-day-on and 4-day-off schedule, and a standard 3+3 design. In the phase II part of the study, 24/33 patients were included to further assess VBDD's safety and efficacy...
April 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29673407/hypercalcemia-as-a-rare-presentation-of-angioimmunoblastic-t-cell-lymphoma-a-case-report
#4
Sana Chams, Inaya Hajj Hussein, Skye El Sayegh, Nour Chams, Khalid Zakaria
BACKGROUND: Angioimmunoblastic T cell lymphoma is a rare malignancy, accounting for only 2% of all non-Hodgkin lymphomas, first described in the 1970s and subsequently accepted as a distinct entity in the current World Health Organization classification. Due to the paucity of this disease, there is still no identifiable etiology, no consistent risk factors, and the pathogenesis remains unclear. CASE PRESENTATION: An 83-year-old Caucasian man presented to an emergency department with palpitations and was found to have atrial fibrillation...
April 20, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29673108/lenalidomide-versus-lenalidomide-dexamethasone-prolonged-treatment-after-second-line-lenalidomide-dexamethasone-induction-in-multiple-myeloma
#5
Johan Lund, Astrid Gruber, Birgitta Lauri, Adil Doganay Duru, Cecilie Blimark, Agneta Swedin, Markus Hansson, Karin Forsberg, Lucia Ahlberg, Conny Carlsson, Anders Waage, Peter Gimsing, Annette Juul Vangsted, Ulf Frølund, Erik Holmberg, Gösta Gahrton, Evren Alici, Mats Hardling, Ulf-Henrik Mellqvist, Hareth Nahi
Lenalidomide (Len) plus dexamethasone (Dex) is approved for the treatment of relapsed or refractory multiple myeloma (RRMM). It is possible that single-agent Len may be effective as prolonged treatment regimen in RRMM once patients demonstrate an initial response to Len+Dex induction. Patients with RRMM who responded to first-line Len+Dex in an observational study (NCT01430546) received up to 24 cycles of either Len (25 mg/day) or Len+Dex (25 mg/day and 40 mg/week) as prolonged treatment in a subsequent phase 2 clinical trial (NCT01450215)...
April 19, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29672885/use-of-depth-of-response-to-predict-progression-free-survival-in-relapsed-or-refractory-multiple-myeloma-evaluation-of-results-from-102-clinical-trials
#6
Naveen Mangal, Ahmed Hamed Salem, Rajeev M Menon, Kevin J Freise
Progression-free survival (PFS) is the standard endpoint for demonstration of clinical effectiveness of novel therapies in relapsed or refractory multiple myeloma (RRMM). However, the long evaluation times for PFS limits its usefulness in the development of new therapies. Therefore, the objective of this analysis was to determine the relationship between response rates and median PFS in RRMM. A database was systematically developed from 268 identified RRMM trials reported from 1999 to 2016. Evaluated covariates for the relationship between response rates and PFS included age, sex, drug class(es), and number of drug classes...
April 19, 2018: Hematological Oncology
https://www.readbyqxmd.com/read/29671785/activation-of-er-stress-dependent-mir-216b-has-a-critical-role-in-salvia-miltiorrhiza-ethanol-extract-induced-apoptosis-in-u266-and-u937-cells
#7
Changmin Kim, Hyo-Sook Song, Hojung Park, Bonglee Kim
Although Salvia miltiorrhiza has been reported to have anti-cancer mechanisms, such as caspase activation, cell cycle arrest, an anti-angiogenesis effect, and Bcl-2 family regulation, its underlying mechanism of endoplasmic reticulum (ER) stress-mediated apoptosis has never been demonstrated. Thus, in this current study, ER stress-related apoptosis via miR-216b of the ethanol extract of Salvia miltiorrhiza (SM) is elucidated for the first time. SM treatment inhibited the viability of U266 and U937 cells in a concentration-dependent manner...
April 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29671193/diagnostic-performance-of-18-f-fdg-pet-ct-and-whole-body-mri-before-and-early-after-treatment-of-multiple-myeloma-a-prospective-comparative-study
#8
Mohammad Abd Alkhalik Basha, Maged Abdel Gelil Hamed, Rania Refaat, Mohamad Zakarya AlAzzazy, Manar A Bessar, Elshaimaa Mohamed Mohamed, Ayman F Ahmed, Heba Fathy Tantawy, Khaled Mohamed Altaher, Ahmed Ali Obaya, Amira Hamed Mohamed Afifi
OBJECTIVE: To determine the diagnostic accuracy of WB-MRI and 18 F-FDG PET/CT in detecting infiltration pattern, disease activity, and response to treatment in patients with multiple myeloma (MM). MATERIALS AND METHODS: Fifty-six patients with confirmed MM were included in the present study for pre-treatment evaluation. Among these individuals, 22 patients were available for the post-treatment evaluation of response to therapy. All patients were imaged with both WB-MRI and 18 F-FDG PET/CT...
April 18, 2018: Japanese Journal of Radiology
https://www.readbyqxmd.com/read/29669947/anti-cd19-car-t-cells-with-high-dose-melphalan-and-autologous-stem-cell-transplantation-for-refractory-multiple-myeloma
#9
Alfred L Garfall, Edward A Stadtmauer, Wei-Ting Hwang, Simon F Lacey, Jan Joseph Melenhorst, Maria Krevvata, Martin P Carroll, William H Matsui, Qiuju Wang, Madhav V Dhodapkar, Kavita Dhodapkar, Rituparna Das, Dan T Vogl, Brendan M Weiss, Adam D Cohen, Patricia A Mangan, Emily C Ayers, Selene Nunez-Cruz, Irina Kulikovskaya, Megan M Davis, Anne Lamontagne, Karen Dengel, Naseem Ds Kerr, Regina M Young, Donald L Siegel, Bruce L Levine, Michael C Milone, Marcela V Maus, Carl H June
BACKGROUND: Multiple myeloma is usually fatal due to serial relapses that become progressively refractory to therapy. CD19 is typically absent on the dominant multiple myeloma cell population but may be present on minor subsets with unique myeloma-propagating properties. To target myeloma-propagating cells, we clinically evaluated autologous T cells transduced with a chimeric antigen receptor (CAR) against CD19 (CTL019). METHODS: Subjects received CTL019 following salvage high-dose melphalan and autologous stem cell transplantation (ASCT)...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29667156/how-we-manage-patients-with-plasmacytomas
#10
REVIEW
Despina Fotiou, Meletios A Dimopoulos, Efstathios Kastritis
PURPOSE OF REVIEW: To discuss the diagnostic approach, treatment options, and future considerations in the management of plasmacytomas, either solitary or in the context of overt multiple myeloma (MM). RECENT FINDINGS: Advanced imaging techniques such as whole-body magnetic resonance imaging and positron emission tomography/computerized tomography are essential for the diagnostic workup of solitary plasmacytomas (SP) to rule out the presence of other disease foci...
April 17, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29666301/fratricide-of-nk-cells-in-daratumumab-therapy-for-multiple-myeloma-overcome-by-ex-vivo-expanded-autologous-nk-cells
#11
Yufeng Wang, Yibo Zhang, Tiffany Hughes, Jianying Zhang, Michael A Caligiuri, Don M Benson, Jianhua Yu
PURPOSE: Daratumumab and its use in combination with other agents is becoming a new standard of care for treatment of multiple myeloma (MM). We mechanistically studied how daratumumab acts on NK cells. EXPERIMENTAL DESIGN: Quantities of NK cells in peripheral blood (PB) and/or bone marrow (BM) of MM patients or healthy donors were examined by flow cytometry. NK cell apoptosis and the associated mechanism were assessed by flow cytometry and immunoblotting. Patients' NK cells were expanded in vitro using feeder cells...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29666084/multiple-myeloma-masquerading-as-diabetic-macular-oedema
#12
Kavitha Rao, Hemanth Murthy, N S Muralidhar, Padmaja Kumari Rani
A 58-year-old man, a known diabetic and hypertensive for 5 years was presented to us with a drop in reading vision in both eyes of 2 months duration. His best-corrected visual acuity was 6/24, N36 in both eyes. Fundus findings revealed moderate non-proliferative diabetic retinopathy with bilateral diffuse macular oedema. When conventional therapy with intravitreal ranibizumab did not alter the clinical picture, we looked into the differential diagnosis of bilateral persistent macular detachments and investigated further...
April 17, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29665944/-current-status-and-challenges-of-car-t-immunotherapy-in-hematologic-malignancies-review
#13
Xin Cheng, Ya-Jie Wang, Shuai Feng, Ya-Yun Wu, Tong-Hua Yang, Xun Lai
The chimeric antigen receptor (CAR) T cell therapy has gradually became a new trend in the treatment of refractory and relapsed hematologic malignancies by developing for 30 years. With the exciting development of genetic engineering, CAR-T technology has subjected to 4 generations of innovation. Structure of CAR-T started from a single signal molecule to 2 or more than 2 co-stimulatory molecules, and then coding the CAR gene or promoter. CAR-T can specifically recognize tumor antigens, and does not be restricted by major histocompatibility complex (MHC), thus making a breakthrough in clinical treatment...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665938/-research-and-applications-progress-of-lenalidomide-in-relapsed-refractory-blood-system-diseases-review
#14
Wen-Jing Fan, Zhi-Qiao Fan, Tao Wu, Hai Bai
Lenalidomide, a novel immunomodulatory agent, is a kind of thalidomide derivatives, which shows a good efficacy and safety for hematological system diseases. This review is aimed to evaluate the efficacy and safety of lenalidomide in treatment of patients with multiple myeloma, chronic lymphocytic leukemia, acute myeloid leukemia, non-Hodgkin's lymphoma, classical Hodgkin's lymphoma and POEMS syndrome at their replased or refractory state. At the same time, this review focuses on the newest clinical research and the latest application progress of lenalidomide for relapsed or refractory hematological system diseases...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665921/-metformin-induces-apoptosis-of-human-multiple-myeloma-cell-u266-through-the-mitochondrial-apoptotic-pathway
#15
Jia-Yin Tong, Chong Wang, Yan-Fang Liu, Wei-Qiong Wang, Qian-Qian Hao, Jie Ma, Ling Sun, Hui Sun
OBJECTIVE: Metformin (Met) can inhibit the proliferation of tumor cells in vitro, its effects on multiple myeloma and action mechanisms have been not yet understood. The purpose of this study was to investigate the effect and molecular mechanism of metformin on human myeloma cells U266. METHODS: U266 cells were treated with different concentration of Met, the MTT was used to detect cell proliferation, the PI staining was used to detect the cell cycle, and the protein expression of BCL-2 family and the release of cytochrome C were assessed by Western blot...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665920/-effect-of-bone-marrow-mesenchymal-stem-cells-in-patients-with-multiple-myelima-on-migration-of-myeloma-cells-in-vitro
#16
Xu-Xia Zhang, Ling-Fang Zhang, Le Liu, Hong-Ling Li
OBJECTIVE: To explore the effect of bone marrow mesenchymal stem cells (MSC) in patients with multiple myeloma(MM) on chemotactic migration of myeloma cells in vitro. METHODS: By in vitro co-culture with diffferent MSC, the myeloma cell U266 was divided into 2 groups: group A in which the U266 cells were co-cultured with normal person MSC (N-MSC) and group B in which the U266 cells were co-cultured with MM-MSC. The expression level of CCR1 in U266 cells, migration rate of U266 cells in Transwell, and the effect of supernantant from co-culture of U266 cells with N-MSC and MM-MSC on the migration in Transwell were compared in condition with or without bortezomib...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665919/-effect-and-clinical-significance-of-bortezomib-and-thalidomide-on-the-memory-t-cells-subsets-and-regulatory-t-cells-in-peripheral-blood-of-patients-with-multiple-myeloma
#17
Ling-Ling Shi, Han-Qing Li, Jian-Gang Mei, Xiao-Gang Zhou, Feng Li, Ping Song, Yong-Ping Zhai
OBJECTIVE: To investigate the effects of bortezomib(BTZ) and thalidomide(TM) on peripheral blood memory T-cells (Tm ) and regulatory T cells(Tregs) in patients with multiple myeloma(MM). METHODS: Eighty-six MM patients received 2 courses of chemotherapy were divided into effective (partial response at least) group (63 cases) and ineffective (no partial response) group (17 cases) according to therapeutic efficacy; these 80 patients were divided into BTZ group (38 cases) and TM group (42 cases) yet according to therapeutic regimens, 20 newly diagnosed MM patients were used as baseline group, 30 healthy volunteers were used as healthy control group...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665918/-inhibitory-effect-of-histone-deacetylase-inhibitor-saha-on-proliferation-of-mouse-multiple-myeloma-cell-line-sp2-0-in-vitro-and-in-vivo
#18
Lei Huo, Chen-Yu Zhang, Yi-Fang Dang, Wan-Jun Zhang, Man-Man Liu, Lu-She Liu, Zun-Min Zhu, Na Fang, Shao-Ping Ji, Kai Sun
OBJECTIVE: To explore the anti-myeloma effect of suberoylanilide hydroxamic acid (SAHA) and on mouse myeloma cell line SP2/0 in vitro and in vivo and its mechanism. METHODS: The inhibitory effect of SAHA on SP2/0 cells was measured by CCK-8 assay,and the apoptosis and cell cycle were analyzed by flow cytometry FACS. The protein expression of Caspase-3 and p53 of SP2/0 cells treated with SAHA were examined by Western blot. Annexin V/7-AAD double staining was performed to detect the apoptosis of SP2/0 induced by SAHA in vitro...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29662618/ectopic-expression-of-transcription-factor-batf3-induces-b-cell-lymphomas-in-a-murine-b-cell-transplantation-model
#19
Christian Weiser, Mina V Petkova, Benjamin Rengstl, Claudia Döring, Dorothee von Laer, Sylvia Hartmann, Ralf Küppers, Martin-Leo Hansmann, Sebastian Newrzela
The mechanisms involved in malignant transformation of mature B and T lymphocytes are still poorly understood. In a previous study, we compared gene expression profiles of the tumor cells of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) to their normal cellular counterparts and found the basic leucine zipper protein ATF-like 3 (BATF3) to be significantly upregulated in the tumor cells of both entities. To assess the oncogenic potential of BATF3 in lymphomagenesis and to dissect the molecular interactions of BATF3 in lymphoma cells, we retrovirally transduced murine mature T and B cells with a BATF3-encoding viral vector and transplanted each population into Rag1-deficient recipients...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29661776/targeting-the-leukemia-antigen-pr1-with-immunotherapy-for-the-treatment-of-multiple-myeloma
#20
Gheath Alatrash, Alexander A Perakis, Celine Kerros, Haley L Peters, Pariya Sukhumalchandra, Mao Zhang, Haroon Jakher, Madhushree Zope, Rebecca S Patenia, Anna Sergeeva, Shuhua Yi, Ken H Young, Anne V Philips, Amanda C Herrmann, Haven R Garber, Na Qiao, Jinsheng Weng, Lisa S St John, Sijie Lu, Karen Clise-Dwyer, Elizabeth A Mittendorf, Qing Ma, Jeffrey J Molldrem
PURPOSE: PR1 is a human leukocyte antigen (HLA)-A2 nonameric peptide derived from neutrophil elastase (NE) and proteinase 3 (P3). We have previously shown that PR1 is cross-presented by solid tumors, leukemia, and antigen presenting cells, including B cells. We have also shown that cross-presentation of PR1 by solid tumors renders them susceptible to killing by PR1-targeting immunotherapies. Since multiple myeloma (MM) is derived from B cells, we investigated whether MM is also capable of PR1 cross-presentation and subsequently capable of being targeted using PR1 immunotherapies...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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